Notch signalling is a potential resistance mechanism of progenitor cells within patient‐derived prostate cultures following ROS‐inducing treatments

Packer, John; Hirst, Adam; Droop, Alastair; Adamson, Rachel; Simms, Matthew; Mann, Vincent M.; Frame, Fiona M.; O’Connell, Deborah; Maitland, Norman J.

doi:10.1002/1873-3468.13589

Cited by 13 publications

(15 citation statements)

References 51 publications

(61 reference statements)

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“…For example, as discussed earlier, WNT signaling [ 65 ] is detected after ENZA treatment, and elevated NOTCH signaling is also seen within 4 hours of the start of enzalutamide treatment in vitro [ 64 ]. Rather than indicating increased cell replication, malignancy or tumor progression, NOTCH expression may act to preserve a population of stem-like cells, as seen, for example, after radiotherapy treatments in glioblastoma [ 164 ] and human prostate [ 165 ].…”

Section: Cellular Heterogeneity and Resistance To Androgen Blockadmentioning

confidence: 99%

Resistance to Antiandrogens in Prostate Cancer: Is It Inevitable, Intrinsic or Induced?

Maitland

2021

Cancers

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Increasingly sophisticated therapies for chemical castration dominate first-line treatments for locally advanced prostate cancer. However, androgen deprivation therapy (ADT) offers little prospect of a cure, as resistant tumors emerge rather rapidly, normally within 30 months. Cells have multiple mechanisms of resistance to even the most sophisticated drug regimes, and both tumor cell heterogeneity in prostate cancer and the multiple salvage pathways result in castration-resistant disease related genetically to the original hormone-naive cancer. The timing and mechanisms of cell death after ADT for prostate cancer are not well understood, and off-target effects after long-term ADT due to functional extra-prostatic expression of the androgen receptor protein are now increasingly being recorded. Our knowledge of how these widely used treatments fail at a biological level in patients is deficient. In this review, I will discuss whether there are pre-existing drug-resistant cells in a tumor mass, or whether resistance is induced/selected by the ADT. Equally, what is the cell of origin of this resistance, and does it differ from the treatment-naïve tumor cells by differentiation or dedifferentiation? Conflicting evidence also emerges from studies in the range of biological systems and species employed to answer this key question. It is only by improving our understanding of this aspect of treatment and not simply devising another new means of androgen inhibition that we can improve patient outcomes.

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Section: Cellular Heterogeneity and Resistance To Androgen Blockadmentioning

confidence: 99%

Resistance to Antiandrogens in Prostate Cancer: Is It Inevitable, Intrinsic or Induced?

Maitland

2021

Cancers

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“…To controllably damage the DNA tiles we used low temperature plasma (LTP, figure 1(e)), to investigate how damage to the DNA structure changes the available intercalation sites. LTP, a partially ionised gas and electrically neutral state of matter, is known to induce DNA damage via single-and double-strand breaks [23][24][25] in a treatment time-dependent [23,26] manner. LTPs have thus been developed for various therapeutics [24,25].…”

Section: Introductionmentioning

confidence: 99%

Biophysical characterisation of DNA origami nanostructures reveals inaccessibility to intercalation binding sites

et al. 2020

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Intercalation of drug molecules into synthetic DNA nanostructures formed through selfassembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.

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“…Atmospheric Pressure Plasma Jets (APPJs) have attracted significant interest due to their application potential, such as in potential cancer treatments and wound healing [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15], plasma chemical [16][17][18] and material synthesis [19,20], and surface modifications like thin film deposition [21,22], etching of photoresist [23], and pretreatment of plastic surfaces [24]. The main motivation of these plasma sources for technological applications stems from their ability to generate and deliver reactive atomic and molecular species (both long-and short-lived), along with other active components such as UV, charged particles, and electric fields, under ambient conditions to a target.…”

Section: Introductionmentioning

confidence: 99%

Reproducibility of `COST Reference Microplasma Jets'

Riedel,

Golda,

Held

et al. 2020

Preprint

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Atmospheric pressure plasmas have been ground-breaking for plasma science and technologies, due to their significant application potential in many fields, including medicinal, biological, and environmental applications. This is predominantly due to their efficient production and delivery of chemically reactive species under ambient conditions. One of the challenges in progressing the field is comparing plasma sources and results across the community and the literature. To address this a reference plasma source was established during the 'Biomedical Applications of Atmospheric Pressure Plasmas' EU COST Action MP1101. It is crucial that reference sources are reproducible. Here, we present the reproducibility and variance across multiple sources through examining various characteristics, including: absolute atomic oxygen densities, absolute ozone densities, electrical characteristics, optical emission spectroscopy, temperature measurements, and bactericidal activity. The measurements demonstrate that the tested COST jets are reproducible, within the standard deviation, for each measurement.

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Notch signalling is a potential resistance mechanism of progenitor cells within patient‐derived prostate cultures following ROS‐inducing treatments

Cited by 13 publications

References 51 publications

Resistance to Antiandrogens in Prostate Cancer: Is It Inevitable, Intrinsic or Induced?

Resistance to Antiandrogens in Prostate Cancer: Is It Inevitable, Intrinsic or Induced?

Biophysical characterisation of DNA origami nanostructures reveals inaccessibility to intercalation binding sites

Reproducibility of `COST Reference Microplasma Jets'

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