| 1. |
- Abrahamsson, Per-Anders, et al.
(author)
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Factors Predicting the Off-treatment Duration in Patients with Prostate Cancer Receiving Degarelix as Intermittent Androgen Deprivation Therapy
- 2017
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In: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 3:4-5, s. 470-479
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Journal article (peer-reviewed)abstract
- Background: Intermittent androgen deprivation therapy (IAD) is commonly used in prostate cancer because of the benefits of the off-treatment period (OTP). The off-treatment time for patients depends on cancer progression, often measured as a rise in prostate-specific antigen (PSA). Objective: To evaluate if certain factors can predict OTP duration following 7-mo degarelix therapy. Design, setting, and participants: This multivariable analysis included 191 prostate cancer patients with baseline PSA 4–50 ng/ml or PSA doubling time <24 mo entering the first OTP with PSA ≤4 ng/ml and testosterone <0.5 ng/ml. OTP continued until disease progression, measured as PSA >4 ng/ml. Despite a study-defined OTP maximum of 24 mo, a 50% failure rate was not observed within certain strata. A Weibull distribution was used to estimate median time to PSA >4 ng/ml adjusted for the following variables: age; baseline (or end of induction period [EOI]) PSA; baseline testosterone; cancer stage/previous curative treatment; and Gleason score. According to the results and the utility of these factors in clinical practice, the model was reduced in a stepwise manner. Time to testosterone recovery (testosterone >0.5 and >2.2 ng/ml) was estimated in a similar manner. Results: The full five-factor model showed that baseline PSA (p < 0.0001), age (p = 0.004), prostate cancer stage/previous therapy (p = 0.023), and baseline testosterone (p = 0.039) influenced OTP. A reduced two-factor model (baseline PSA, age) showed that only baseline PSA influenced OTP (p < 0.0001), and patients with baseline PSA ≤4 ng/ml had the longest OTP. In addition, EOI PSA (p < 0.0001) and age (p = 0.050) significantly influenced OTP. The times to testosterone >0.5 and >2.2 ng/ml were longer for older patients and those with lower baseline testosterone levels. Conclusion: Patients with lower baseline and EOI PSA, and older patients can stay off therapy longer and therefore may benefit more from degarelix IAD. These factors may help in proposing an algorithm to predict the OTP and optimise visit frequency. Patient summary: We describe extended analysis results for a trial in which patients with prostate cancer received intermittent androgen deprivation treatment. Prostate-specific antigen levels at baseline and at the end of the induction period, as well as older age, predicted the duration of the off-treatment period. Testosterone recovery was slower in older patients and in patients who had lower pretreatment testosterone levels. These factors may help in deciding whether to choose continuous or intermittent treatment as a strategy. Trial registration: Clinicaltrials.gov NCT00801242 Age and prostate-specific antigen levels before and at the end of active treatment seem to predict off-treatment duration for degarelix as intermittent androgen deprivation treatment (ADT). This information could be valuable in proposing an algorithm to predict the off-treatment period, optimise visit schedules, and set the restart sate for ADT.
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| 2. |
- Canesin, Giacomo, et al.
(author)
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STAT3 inhibition with galiellalactone effectively targets the prostate cancer stem-like cell population
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Cancer stem cells (CSCs) are a small subpopulation of quiescent cells with the potential to differentiate into tumor cells. CSCs are involved in tumor initiation and progression and contribute to treatment failure through their intrinsic resistance to chemo- or radiotherapy, thus representing a substantial concern for cancer treatment. Prostate CSCs’ activity has been shown to be regulated by the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Here we investigated the effect of galiellalactone (GL), a direct STAT3 inhibitor, on CSCs derived from prostate cancer patients, on docetaxel-resistant spheres with stem cell characteristics, on CSCs obtained from the DU145 cell line in vitro and on DU145 tumors in vivo. We found that GL significantly reduced the viability of docetaxel-resistant and patient-derived spheres. Moreover, CSCs isolated from DU145 cells were sensitive to low concentrations of GL, and the treatment with GL suppressed their viability and their ability to form colonies and spheres. STAT3 inhibition down regulated transcriptional targets of STAT3 in these cells, indicating STAT3 activity in CSCs. Our results indicate that GL can target the prostate stem cell niche in patient-derived cells, in docetaxel-resistant spheres and in an in vitro model. We conclude that GL represents a promising therapeutic approach for prostate cancer patients, as it reduces the viability of prostate cancer-therapy-resistant cells in both CSCs and non-CSC populations.
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| 3. |
- Wang, Lei, et al.
(author)
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Circularly Polarized Compact LTSA Array in SIW Technology
- 2017
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In: IEEE Transactions on Antennas and Propagation. - : IEEE. - 0018-926X .- 1558-2221. ; 65:6, s. 3247-3252
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Journal article (peer-reviewed)abstract
- Typical linearly tapered slot antenna (LTSA) usually features a wideband and a high gain. However, its geometry size is large, especially very long in the tapering direction, which limits its application in compact antenna and array systems. This communication has minimized the tapered length to less than 0.19 lambda(0) when the aperture width is less than 0.35 lambda(0) both for horizontally and vertically polarized LTSA arrays. Moreover, the typical polarization of the LTSA is linear, which is perpendicular to the slot. In this communication, an X-band circularly polarized 1x8 LTSA array, made of cross-LTSAs, is proposed with the feeding of a substrate integrated waveguide horn. All the three different polarized LTSA arrays are designed and investigated both in simulation and experiment, and the simulation results agree well with the measured results.
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