scholarly journals Optimizing the Pharmacological and Optical Dosimetry for Photodynamic Therapy with Methylene Blue and Nanoliposomal Benzoporphyrin on Pancreatic Cancer Spheroids

Onco ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 19-33
Author(s):  
Tristan Le Clainche ◽  
Nazareth Milagros Carigga Gutierrez ◽  
Núria Pujol-Solé ◽  
Jean-Luc Coll ◽  
Mans Broekgaarden
Keyword(s):  
Pancreatic Cancer ◽  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Optical Parameters ◽  
Light Dosimetry ◽  
Radiant Exposure ◽  
Pancreatic Cancer Cells ◽  
Suitable Treatment ◽  
Cancer Spheroids ◽  
Cancer Tissues

Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers are hydrophobic molecules, nanoliposomes are frequently used to increase the biocompatibility of these therapeutics. However, as nanoliposomes can influence the therapeutic performance of photosensitizers, the most suitable treatment parameters need to be elucidated. Here, we evaluate the efficacy of PDT on spheroid cultures of PANC-1 and MIA PaCa-2 pancreatic cancer cells. Two strategies to photosensitize the pancreatic microtumors were selected, based on either nanoliposomal benzoporphyrin derivative (BPD), or non-liposomal methylene blue (MB). Using a comprehensive image-based assay, our findings show that the PDT efficacy manifests in distinct manners for each photosensitizer. Moreover, the efficacy of each photosensitizer is differentially influenced by the photosensitizer dose, the light dose (radiant exposure or fluence in J/cm2), and the dose rate (fluence rate in mW/cm2). Taken together, our findings illustrate that the most suitable light dosimetry for PDT strongly depends on the selected photosensitization strategy. The PDT dose parameters should therefore always be carefully optimized for different models of cancer.

scholarly journals Alkynyl N-BODIPYs as Reactive Intermediates for the Development of Dyes for Biophotonics

2020 ◽  
Vol 3 (1) ◽  
pp. 15
Author(s):  
César Ray ◽  
Andrés García-Sampedro ◽  
Christopher Schad ◽  
Edurne Avellanal-Zaballa ◽  
Florencio Moreno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Click Chemistry ◽  
Cancer Cells ◽  
Reactive Intermediates ◽  
New Approach ◽  
Pancreatic Cancer Cells ◽  
Bio Imaging

A new approach for the rapid multi-functionalization of BODIPY dyes towards biophotonics is reported. It is based on novel N-BODIPYs, through reactive intermediates with alkynyl groups to be further derivatized by click chemistry. This approach has been exemplified by the development of new dyes for cell bio-imaging, which have proven to successfully internalize into pancreatic cancer cells and accumulate in the mitochondria. The in vitro suitability for photodynamic therapy (PDT) was also analyzed and confirmed our compounds to be promising PDT candidates for the treatment of pancreatic cancer.

scholarly journals YOD1 Serves as a Potential Prognostic Biomarker For Pancreatic Cancer

2021 ◽  
Author(s):  
Zhishuo Zhang ◽  
Wenxia Zhao ◽  
Yiming Li ◽  
Yang Li ◽  
Yang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Expression Level ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Post Translational Modification ◽  
Pancreatic Cancer Cells ◽  
Proliferation And Metastasis ◽  
Cancer Tissues

Abstract Background Ubiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect, biological function and mechanism of YOD1 in pancreatic cancer are still unclear. ResultsIn the GEO and TCGA databases, YOD1 mRNA expression is significantly up-regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up-regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P<0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8+ T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell and Western blot indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells.Conclusion Our results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.

scholarly journals CircRHOT1 Mediated Cell Proliferation, Apoptosis and Invasion of Pancreatic Cancer Cells by Sponging miR-125a-3p

2020 ◽  
Author(s):  
Sunkai Ling ◽  
Yanru He ◽  
Xiaoxue Li ◽  
Mingyue Hu ◽  
Yu Ma ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Biological Function ◽  
Diagnostic Marker ◽  
Biological Functions ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

Abstract Background: The present study aimed to investigate the mechanistic biological function of circRHOT1 in pancreatic cancer cells.Methods: The expression of circRHOT1 and miR-125a-3p in pancreatic cancer tissues and their paired adjacent normal tissues was quantified by qRT-PCR. By knocking down or overexpressing circRHOT1 and miR-125a-3p in pancreatic cancer cells, their functions and potential mechanisms were explored.Results: circRHOT1 was overexpressed in pancreatic cancer tissues and cell lines, and it was found to directly bind to miR-125a-3p, acting as an endogenous sponge to inhibit its activity. Knockdown of circRHOT1 expression significantly inhibited proliferation as well as invasion, and it promoted apoptosis of pancreatic cancer cells via the regulation of E2F3 through the targeting of miR-125a-3p.Conclusion: Taken together, our results demonstrated that circRHOT1 plays critical roles in regulating the biological functions of pancreatic cancer cells, suggesting that circRHOT1 may serve as a potential diagnostic marker and therapeutic target for patients with pancreatic cancer.

scholarly journals TM4SF1 Regulates Pancreatic Cancer Migration and Invasion In Vitro and In Vivo

2016 ◽  
Vol 39 (2) ◽  
pp. 740-750 ◽  
Author(s):  
Jia Cao ◽  
Jia-chun Yang ◽  
Vijaya Ramachandran ◽  
Thiruvengadam Arumugam ◽  
De-feng Deng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Tumor ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues ◽  
Immunohistochemical Analyses ◽  
Expression And Activity

Background/Aims: The cell surface protein transmembrane 4 L6 family member 1 (TM4SF1) has been detected in various tumors and plays a major role in the development of cancer. We aimed to investigate the effects of TM4SF1 on the migration and invasion of pancreatic cancer in vitro and in vivo and explore its related molecular mechanisms. Methods: qRT-PCR and immunohistochemical analyses were used to measure the expression of TM4SF1 in pancreatic cancer tissues and adjacent tissues. TM4SF1 was silenced using siRNA and shRNA to investigate the role of this protein in the proliferation and metastasis of pancreatic cancer cells. MTS and Transwell assays were used to examine the effect of TM4SF1 on pancreatic cancer cell lines. The expression and activity of MMP-2 and MMP-9 were determined by qRT-PCR, western blots and gelatin zymography. In vivo, orthotopic pancreatic tumor models were used to examine the formation of metastasis. Results: qRT-PCR and immunohistochemical analyses showed that TM4SF1 was highly expressed in pancreatic cancer tissues compared with the adjacent tissues. In in vitro experiments the silencing of TM4SF1 reduced cell migration and invasion and down-regulated the expression and activity of MMP-2 and MMP-9. However, no significant difference in cell proliferation was detected after silencing TM4SF1. Additionally, knocking down TM4SF1 decreased the formation of lung and liver metastases in orthotopic pancreatic tumor models. Conclusion: Our results demonstrate that the expression of TM4SF1 is higher in pancreatic cancer tissues and pancreatic cancer cell lines than controls. Knockdown of TM4SF1 inhibited the migration and invasion of pancreatic cancer cells by regulating the expression and activity of MMP-2 and MMP-9, which suggests that TM4SF1 may play a significant role in metastasis in pancreatic cancer.

scholarly journals SIRT1 promotes the proliferation and metastasis of human pancreatic cancer cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769118 ◽  
Author(s):  
Jianguang Jin ◽  
Zhijie Chu ◽  
Pengfei Ma ◽  
Yuanpu Meng ◽  
Yanhui Yang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Pancreatic Cancer Cells ◽  
Cell Proliferation And Migration ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

SIRT1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SIRT1 promotes pancreatic cancer tumorigenesis. The aim of this study is to investigate the SIRT1 expression levels and biological functions in promoting pancreatic cancer progression. We first investigated the expression of SIRT1 in a series of pancreatic cancer tissues as well as in a panel of pancreatic cancer cell lines. The effect of SIRT1 on cell activity was explored by knockdown experiments. Cell growth was measured using the MTT assay and colony-formation assay. Migration and invasion were tested using transwell assay. Our results showed that the expression of SIRT1 was significantly up-regulated both in pancreatic cancer tissues and cell lines. Knockdown of SIRT1 suppressed cell proliferation and migration of pancreatic cancer cells. This is the first report to disclose the role of SIRT1 in regulation of pancreatic cancer cell proliferation and migration, which may provide a potential therapeutic target for pancreatic cancer patients.

scholarly journals CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yankun Chen ◽  
Simiao Xu ◽  
Xinyuan Liu ◽  
Xueyi Jiang ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Diagnosis And Prognosis ◽  
Pancreatic Cancer Cells ◽  
Invasive Capacity ◽  
And Migration ◽  
Cancer Tissues

Abstract Background Circular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. It played different roles in a variety of diseases including cancer and performed different functions. Nonetheless, reports on the specific function of circRNA in pancreatic cancer (PC) were still rarely so far. In particular, the role of circSEC24A in PC remains unclear. Methods Real-time fluorescent quantitative PCR was used to evaluate the expression level of circSEC24A in pancreatic cancer tissues and cell lines. Furthermore, we used some functional experiments, such as EDU and Transwell assays, to explore the effects of circSEC24A on the proliferation and invasiveness of pancreatic cancer. Finally, the corresponding relationship among circSEC24A, miR-606 and TGFBR2 was explored by dual luciferase reporter and other mechanism studies. Results The expression of circSEC24A in both pancreatic cancer tissues and cell lines was evidently up-regulated. Furthermore, knockdown of circSEC24A significantly inhibited the proliferative, migration and invasive capacity of pancreatic cancer cells, whereas miR-606 inhibitor obviously counteracted these effects. Further study confirmed that circSEC24A alleviated suppression on target TGFBR2 expression by directly sponging miR-606 and then influenced the tumorigenesis of pancreatic cancer. Conclusions These findings indicated that the progression of pancreatic cancer can be driven by circSEC24A influencing miR-606/TGFBR2 axis. Therefore, circSEC24A might be used as a critical biomarker influencing the early diagnosis and prognosis of pancreatic cancer.

scholarly journals CircRNA_000864 Upregulates B-cell Translocation Gene 2 Expression and Represses Migration and Invasion in Pancreatic Cancer Cells by Binding to miR-361-3p

2020 ◽  
Vol 10 ◽  
Author(s):  
Linsheng Huang ◽  
Junxiang Han ◽  
Huifan Yu ◽  
Jialing Liu ◽  
Lili Gui ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Pancreatic Cancer Cells ◽  
Gene Assay ◽  
Cancer Tissues

BackgroundPancreatic cancer is a fatal disease with a very poor prognosis due to its characteristic insidious symptoms, early metastasis, and chemoresistance. Circular RNAs (circRNAs) are involved in the development of pancreatic cancer.AimHence, the aim of this study is to elucidate the mechanism of circRNA_000864 in regulating BTG2 expression in pancreatic cancer by binding to miR-361-3p.MethodsCircRNA_000864, miR-361-3p, and BTG2 expression patterns in the pancreatic cancer tissues were detected by RT-qPCR. Correlation among circRNA_000864, miR-361-3p, and BTG2 was evaluated by RNA-pull down assay, RNA Immunoprecipitation assay, and dual-luciferase reporter gene assay. After ectopic expression and depletion experiments, 5-ethynyl-2′-deoxyuridine assay, Transwell assay, and flow cytometry were employed to assess the cell proliferation, migration and invasion, cell cycle, and apoptosis. Xenotransplantation of nude mice was conducted to detect the effects of circRNA_000864, miR-361-3p, and BTG2 on tumor growth.ResultsCircRNA_000864 and BTG2 were poorly expressed, and miR-361-3p was highly expressed in the pancreatic cancer tissues. CircRNA_000864 bound to miR-361-3p could target BTG2. Cell proliferation, migration, and invasion were inhibited, and the cell cycle arrest and apoptosis were stimulated after overexpression of circRNA_000864 or BTG2 or downregulation of miR-361-3p. Overexpression of circRNA_000864 or downregulation of miR-361-3p also decreased the tumor growth in vivo.ConclusionsConjointly, our findings elicited that the overexpression of circRNA_000864 could promote BTG2 expression to inhibit pancreatic cancer development by binding to miR-361-3p, which represents an appealing therapeutic target for the treatment of pancreatic cancer.

MicroRNA-296-5p Promotes Cell Invasion and Drug Resistance by Targeting Bcl2-Related Ovarian Killer, Leading to a Poor Prognosis in Pancreatic Cancer

Digestion ◽  
2019 ◽  
Vol 101 (6) ◽  
pp. 794-806 ◽  
Author(s):  
Jun Okazaki ◽  
Toshihito Tanahashi ◽  
Yasushi Sato ◽  
Jinsei Miyoshi ◽  
Tadahiko Nakagawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Poor Prognosis ◽  
Cancer Cell Lines ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

<b><i>Background/Aims:</i></b> Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive invasion, early metastasis, and resistance to chemotherapy, leading to a poor prognosis. To clarify the molecular mechanism of these malignant characteristics, we performed a genome-wide microRNA (miRNA) array analysis utilizing micro-cancer tissues from patients with unresectable PDAC (stage IV), obtained by endoscopic ultrasound-fine needle aspiration (EUS-FNA). <b><i>Methods:</i></b> The expression profiles of 2,042 miRNAs were determined using micro-cancer tissues from 13 patients with unresectable PDAC obtained by EUS-FNA. The relationship between individual miRNA levels and overall survival (OS) was analyzed. Possible target genes for miRNAs were bioinformatically analyzed using the online database miRDB. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and PK-8 were transfected with miRNA mimic or small interfering RNA, and cell invasion, epithelial-mesenchymal transition (EMT), and apoptosis markers were examined. miRNA and mRNA expressions were examined by quantitative polymerase chain reaction. <b><i>Results:</i></b> Of 2,042 miRNAs, the 10 that exhibited the lowest correlation coefficient (<i>p</i> ≤ 0.005) between miRNA expression level and OS among the patients were identified. The miRDB and expression analysis in cancer cell lines for the 10 miRNAs identified miR-296-5p and miR-1207-5p as biomarkers predictive of shorter survival (<i>p</i> &#x3c; 0.0005). Bioinformative target gene analysis and transfection experiments with miRNA mimics showed that <i>Bcl2-related</i> <i>ovarian</i> <i>killer</i> (<i>BOK</i>), a pro-apoptotic gene, is a target for miR296-5p in pancreatic cancer cells; transfection of miR-296-5p mimic into PANC-1, MIA PaCa-2, and PK-8 cells resulted in significant suppression of <i>BOK</i> mRNA and protein expression. These transfectants showed significantly higher invasion capability compared with control cells, and knock down of <i>BOK</i> in pancreatic cancer cells similarly enhanced invasion capability. Transfectants of miR-296-5p mimic also exhibited aberrant expression of EMT markers, including vimentin and N-cadherin. Moreover, these transfectants showed a significantly lower apoptosis rate in response to 5-fluorouracil and gemcitabine with a decrease of <i>BOK</i> expression, suggesting a role of miR-296-5p in drug resistance. <b><i>Conclusion:</i></b> These results suggest that miR-296-5p is a useful biomarker for a poor prognosis in patients with PDAC, and that the miR-296-5p/BOK signaling axis plays an important role in cell invasion, drug resistance, and EMT in PDACs.

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