Prostate cancer (pca) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management ...typically includes the combination of long-term androgen deprivation therapy (adt) and radiotherapy (rt). New androgen-receptor-axis targeted therapies (arats), which await validation, offer an option to intensify therapy.
In this narrative review, we report the relevant history that has supported combining adt with rt. The literature in PubMed was searched for studies involving pca and novel arats (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored.
Early results from three phase i/ii trials demonstrated that concurrent abiraterone acetate, adt, and rt is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single
study implies synergy for radiosensitization beyond that facilitated by conventional adt. Studies investigating the combination of other arats with rt are under way, including multiple phase iii trials, but short-term results are not yet available.
ABSTRACT
Trichinella spiralis (T. spiralis) is an immunomodulating parasite that can adversely affect tumor growth and extend host lifespan. The aim of this study was to elucidate the mechanisms by ...which T. spiralis larval antigens achieve this effect using Ehrlich solid carcinoma (ESC) murine model. Assessment was done by histopathological and immunohistochemical analysis of caspase‐3, TNF‐α, Ki‐67 and CD31. Additionally, Bcl2 and Bcl2‐associated protein X (Bax) relative gene expression was assessed by molecular analysis for studying the effect of T. spiralis crude larval extract (CLE) antigen on tumor necrosis, apoptosis, cell proliferation and angiogenesis. We found that both T. spiralis infection and CLE caused a decrease in the areas of necrosis in ESC. Moreover, they led to increased apoptosis through activation of caspase‐3, up‐regulation of pro‐apoptotic gene, Bax and down‐regulation of anti‐apoptotic gene, Bcl2. Also, T. spiralis infection and CLE diminished ESC proliferation, as evidenced by decreasing Ki‐67. T. spiralis infection and CLE were able to suppress the development of ESC by inhibiting tumor proliferation, inducing apoptosis and decreasing tumor necrosis, with subsequent decrease in tumor metastasis. T. spiralis CLE antigen may be considered as a promising complementary immunotherapeutic agent in the treatment of cancer.
Donor-acceptor conjugated polymers are considered advanced semiconductor materials for the development of thin-film electronics. One of the most attractive families of polymeric semiconductors in ...terms of photovoltaic applications are benzodithiophene-based polymers owing to their highly tunable electronic and physicochemical properties, and readily scalable production. In this work, we report the synthesis of three novel push-pull benzodithiophene-based polymers with different side chains and their investigation as hole transport materials (HTM) in perovskite solar cells (PSCs). It is shown that polymer
that contains triisopropylsilyl side groups exhibits better film-forming ability that, along with high hole mobilities, results in increased characteristics of PSCs. Encouraging a power conversion efficiency (PCE) of 17.4% was achieved for
-based PSCs that outperformed the efficiency of devices based on
,
, and benchmark PTAA polymer. These findings feature the great potential of benzodithiophene-based conjugated polymers as dopant-free HTMs for the fabrication of efficient perovskite solar cells.
Renal dysfunction is a common complication of MM and is associated with poor prognosis, particularly when progressive. Early identification of renal dysfunction is essential for prompt treatment for ...disease control and restoration of renal function. Urinary insulin-like growth factor-binding protein 7 (IGFBP-7), urinary tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and serum transgelin levels were measured using enzyme-linked immunosorbent assays and evaluated as biomarkers for the prediction of renal impairment in patients with multiple myeloma. U
IGFBP-7/creatinine
ratio, U
TIMP2/creatinine
ratio, and serum transgelin levels were higher in patients with MM than healthy controls, and predicted renal insufficiency in MM. Serum transgelin, urinary IGFBp7, and TIMP2 levels may have utility as biomarkers of renal tubular injury and predict future renal impairment in patients with MM.
Purpose: To report the long-term outcomes of the McGill 0913 study and the potential benefits of combining prostate-bed radiotherapy (PBRT), pelvic-lymph-node radiotherapy (PLNRT), and long term ADT ...(LT-ADT). Materials and Methods: From 2010 to 2016, 46 high-risk prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy (RP) were enrolled in this single-arm phase II clinical trial. The patients were eligible if they had a Gleason score > 8, locally advanced disease (≥pT3), a preoperative PSA of >20 ng/mL, or positive lymph nodes (LN). The patients were treated with a combination of 24 months of ADT, PBRT, and PLNRT. The primary outcome was biochemical progression-free survival (bPFS) and the predefined secondary endpoints included distant-metastasis-free survival (DMFS), overall survival (OS), and toxicity. In this update, we also report the median follow-up of 8.8 years and 10 years OS. Results: At a median follow-up of 8.8 years, 43 patients were eligible for analysis. The median pre-salvage PSA was 0.30 μg/L. Half (51%) of the patients (n = 22) had positive margins, 40% (n = 17) had Gleason scores > 8, 63% (n = 27) had extracapsular extension, 42% (n = 18) had seminal vesicle invasion, and 19% (n = 8) had LN involvement. The 10-year bPFS was 68.3 %. The 10-year DMFS was 72.9%. The 10-year OS was 97%. There were two non-cancer-related deaths. The first patient died of congestive heart failure while the other died of an unknown cause. No new toxicity was observed after the initial report. Conclusions: Our study demonstrates that treatment escalation with PBRT, PLNRT, and LT-ADT improves long term outcomes. In view of the recently published SPPORT study, we conclude that this novel approach of treatment intensification in high-risk post-prostatectomy patients is safe and effective, and that it should be offered as the standard of care.
Purpose/objectives
High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, ...data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure.
Materials/methods
We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered
via
intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis.
Results
From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT
via
conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%.
Conclusions
To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.
In this paper, emission spectra of both positive column (PC) and negative glow (NG) regions of the dc glow discharge have been measured at different pressures and currents. The intensity of the lines ...in the NG is in the order of five times of that corresponding lines' intensity in the PC region. It is found that the line intensity increases linearly with the discharge current, while it increases as P alpha with the gas pressure. The electron temperature T e has been estimated using the line-to-line-intensity-ratio technique. It is found that T e derived by this technique generally decreases with the pressure. Also, T e in NG region is about 3/2 of that in the PC
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