Genetic factors affecting patient responses to pancreatic cancer treatment

Fotopoulos, George; Syrigos, Konstantinos; Saif, Muhammad Wasif

doi:10.20524/aog.2016.0056

Cited by 5 publications

(6 citation statements)

References 70 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, because of its late diagnosis, surgery is a viable option to less than 20% of cases [5]. Chemotherapy drugs for PaCa include gemcitabine, 5-fluorouracil, cisplatin, and paclitaxel [6, 7]. These cytotoxic therapies have a number of negative side effects including low blood count and peripheral neuropathy [8].…”

Section: Introductionmentioning

confidence: 99%

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors

Hurtado

Sankpal

Kaba

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated. Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks. Results: The IC₅₀ value for Cu-TA was about half than TA.Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G₂/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring. Conclusion: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth.

show abstract

Section: Introductionmentioning

confidence: 99%

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors

Hurtado

Sankpal

Kaba

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“… 5 , 6 Previous studies have demonstrated that mutations in different genes such as K‐RAS, hENT1, DCK, CDA, HMLH1, TP1DPD, HER2 and SMAD4, could drive the development of PC chemoresistance. 7 However, the identified genetic alterations cannot fully explain the chemoresistance observed in PC and mounting data suggested that non‐genetic mechanisms, including microRNAs (miRNAs) and circular RNAs (circRNAs), are also implicated in chemoresistance development and treatment response. 8 For instance, increasing number of circRNAs have been involved in PC chemoresistance through high‐throughput sequencing studies.…”

Section: Introductionmentioning

confidence: 99%

“…The complicated aetiology of PC tumorigenesis and chemoresistance has been revealed through the application of next‐generation sequencing technology 5,6 . Previous studies have demonstrated that mutations in different genes such as K‐RAS, hENT1, DCK, CDA, HMLH1, TP1DPD, HER2 and SMAD4, could drive the development of PC chemoresistance 7 . However, the identified genetic alterations cannot fully explain the chemoresistance observed in PC and mounting data suggested that non‐genetic mechanisms, including microRNAs (miRNAs) and circular RNAs (circRNAs), are also implicated in chemoresistance development and treatment response 8 .…”

Section: Introductionmentioning

confidence: 99%

Resistance to gemcitabine is mediated by the circ_0036627/miR‐145/S100A16 axis in pancreatic cancer

Yu,

Wang,

Zhang

et al. 2024

J Cellular Molecular Medi

View full text Add to dashboard Cite

The development of gemcitabine (GEM) resistance severely limits the treatment efficacy in pancreatic cancer (PC) and increasing evidence highlights the vital roles of circular RNAs (circRNAs) in the tumorigenesis, progression and drug resistance of PC. However, the circRNAs underlying GEM resistance development of PC remains to be clarified. The current research aims to unveil the roles of circ_0036627 in dictating the aggressiveness and GEM sensitivity in PC. We reported the increased expression of circ_0036627 in PC tissues and PC cell lines. Elevated circ_0036627 expression level was correlated with advanced tumour grade and poor overall survival in PC patients. Functional assays and in vivo experiments demonstrated that circ_0036627 overexpression was required for the proliferation, migration invasion and GEM resistance in PC cells. circ_0036627 knockdown suppressed tumour development in vivo. The molecular analysis further showed that circ_0036627 increased S100A16 expression by sponging microRNA‐145 (miR‐145), a tumour‐suppressive miRNA that could significantly attenuate PC cell proliferation, migration, invasion and GEM resistance. Furthermore, our findings suggested that S100A16 acted as an oncogenic factor to promote aggressiveness and GEM resistance in PC cells. In conclusion, the current findings provide new mechanistic insights into PC aggressiveness and GEM resistance, suggesting the critical role of circ_0036627/miR‐145/S100A16 axis in PC progression and drug resistance development and offering novel therapeutic targets for PC therapy.

show abstract

“…The detection of DNA fragments with specific sequences has applications in the diagnosis of infectious diseases (1) and genetic diseases, (2) as well as in precision medicine. (3) In the case of genetic diseases, early diagnosis allows prompt medical treatment before disease progression. (4) Genetic diagnosis has become increasingly important, as it helps to prevent the onset of disease before occurrence.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Probe DNA Immobilization Method for Label-free DNA Biosensing Using Polymer-based Photonic Crystal

Nishitsuji¹,

Sueyoshi²,

Hisamoto³

et al. 2023

Sensors and Materials

View full text Add to dashboard Cite

Polymer-based photonic crystals (PhCs) were fabricated using nanoimprint lithography for use as DNA biosensors by immobilizing the probe DNA. Polymer-based PhCs can be applied to cost-effective and label-free DNA biosensors. Additionally, DNA hybridization can be detected using inexpensive and simple optical systems. In this study, probe DNA was immobilized on the PhC surface using electrostatic adsorption or covalent bonding, and the sensing performance was compared. Consequently, the PhC biosensor prepared using covalent bonding exhibited greater DNA-hybridization-induced reflection intensity changes than that prepared using electrostatic adsorption. Furthermore, discrimination of reflection intensity for target and mismatch DNA was investigated, which revealed that in contrast to the PhC biosensor prepared using the electrostatic adsorption of probe DNA, that prepared using covalent bonding discriminated target DNA at a concentration of 0.1 nM.

show abstract

Genetic factors affecting patient responses to pancreatic cancer treatment

Cited by 5 publications

References 70 publications

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors

Resistance to gemcitabine is mediated by the circ_0036627/miR‐145/S100A16 axis in pancreatic cancer

Investigation of Probe DNA Immobilization Method for Label-free DNA Biosensing Using Polymer-based Photonic Crystal

Contact Info

Product

Resources

About