Ultrasound-Induced Microbubble Cavitation Combined with miR-34a-Loaded Nanoparticles for the Treatment of Castration-Resistant Prostate Cancer

2021 ◽  
Vol 17 (1) ◽  
pp. 78-89
Author(s):  
Ziqi Wang ◽  
Chuanrong Chen ◽  
Yuchen Tao ◽  
Penglin Zou ◽  
Feng Gao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Tumor Tissue ◽  
Cell Membrane Permeability ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
First Line ◽  
Chemotherapy Drugs ◽  
Castration Resistant ◽  
Methoxy Polyethylene Glycol

Currently chemotherapy drugs are usually used as first-line treatments for castration-resistant prostate cancer (CRPC), but they are ineffective and accompanied by serious side effects. MicroRNA-34a (miR-34a) simultaneously targets multiple genes related to the cell apoptosis in CRPC cells without obvious side effects. It has shown great potential in the treatment of CRPC. Previous studies focused on miR-34a increasing the sensitivity of chemotherapy drugs to chemoresistant prostate cancer cells. There are few researches on miR-34a alone in the treatment of CRPC. But the macromolecular miR-34a is difficult to enter the cell and is easily degraded by nuclease. Therefore, we constructed methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles to encapsulate miR-34a (miR-34a/NP). The results showed that miR-34a/NP protects miR-34a from degradation by nucleases and can be phagocytized by PC-3 CRPC cells. Ultrasound induces microbubble cavitation (UIMC) improves cell membrane permeability and capillary gaps, and further promotes miR-34a/NP to enter cells PC-3 and prostate cancer xenografts. The miR-34a/NP that enters the cell and tumor tissue releases miR-34a, which suppressed CRPC cells PC-3 proliferation, promoted its apoptosis, and inhibited the growth of CRPC xenografts. Our research verified that miR-34a/NP, especially combined with UIMC, has a significant anti-tumor effect on CRPC.

scholarly journals Fatigue, quality of life and metabolic changes in men treated with first-line enzalutamide versus abiraterone plus prednisolone for metastatic castration-resistant prostate cancer (HEAT): a randomised trial protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030218
Author(s):  
Klara Kvorning Ternov ◽  
Jens Sønksen ◽  
Mikkel Fode ◽  
Henriette Lindberg ◽  
Caroline Michaela Kistorp ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Adipose Tissue ◽  
Side Effects ◽  
Functional Assessment ◽  
Randomised Trial ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant

IntroductionEnzalutamide and abiraterone acetate plus prednisolone (AAP) are used in combination with androgen-deprivation therapy to further suppress the androgen stimulation of metastatic castration-resistant prostate cancer (mCRPC). First-line mCRPC treatment with enzalutamide and AAP yields similar overall survival and radiographic progression-free survival in phase III trials. Thus, treatment selection relies on patient choice, cost and side effects. The aim of this randomised trial is to investigate differences in fatigue, health-related quality of life (HRQoL) and metabolic side effects in men with mCRPC treated with first-line enzalutamide versus AAP.Methods and analysisIn this ongoing open-label randomised (1:1) clinical trial, enzalutamide is compared with AAP as first-line treatment for men with mCRPC. The primary endpoint is fatigue assessed with the questionnaire Functional Assessment of Chronic Illness Therapy-Fatigue version 4. Secondary endpoints are changes in body composition (ie, fat mass, visceral adipose tissue, subcutaneous adipose tissue and lean body mass assessed with dual energy X-ray absorptiometry), glucose metabolism assessed with a 2-hour oral glucose tolerance test, serum lipids, blood pressure and HRQoL assessed with the questionnaire Functional Assessment of Cancer Therapy-Prostate (FACT-P). All study endpoints are assessed at baseline and 12-week postintervention. Blood and urine samples are collected at baseline and at time of progression on allocated treatment for future investigation of predictive and prognostic biomarkers in prostate cancer treatment. The planned sample size is 170 participants. All participants are recruited from Herlev and Gentofte Hospital, Denmark. Estimated last patient’s last visit is February 2020.Ethics and disseminationThe study received project approval from the National Committee on Health Research Ethics and Danish Data Protection Agency and Danish Medicines Agency (EudraCT no.: 2017-000027-99). The results of the study will be published in peer-reviewed international journals and will be presented at national and international conferences and symposiums.Trial registration numberClinicaltrialsregister.eu (2017-000099-27).

Cabazitaxel in the Management of Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel-based Chemotherapy

2012 ◽  
Vol 08 (01) ◽  
pp. 42 ◽  
Author(s):  
Axel Heidenreich ◽  
David Pfister ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Metastatic Progression ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Patient Counselling ◽  
Castration Resistant

Docetaxel is the guideline-recommended first-line chemotherapy in men with castration-resistant prostate cancer (CRPC). Despite its proven survival benefit, however, all patients will progress after a mean interval of six to eight months. Recently, the FDA approved cabazitaxel and abiraterone acetate as effective second-line treatment options in this clinical scenario. By comparison with mitoxantrone, cabazitaxel improves progression-free survival, overall survival, time to prostate surface antigen (PSA) progression and time to metastatic progression. On the other hand, cabazitaxel (Sanofi) is asscociated with a significantly higher frequency of grade 3 and 4 haematotoxic and gastrointestinal side effects than mitoxantrone. In experienced hands, and with the use of proactive therapeutic measures – such as weekly monitoring, adequate patient counselling and appropriate application of the guidelines on management and prophylaxis of neutropenia and diarrhoea — all side effects can be handled easily without harming the patient, as has been shown recently by the analysis of the results of the German and European compassionate use programmes. Cabazitaxel is one of the key components in the management of disease progression after docetaxel, and might be of benefit in men with high metastatic burden, rapid PSA doubling time and minimal side effects during first-line docetaxel therapy.

Cabazitaxel in the Management of Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel-based Chemotherapy

2012 ◽  
Vol 08 (01) ◽  
pp. 61
Author(s):  
Axel Heidenreich ◽  
David Pfister ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Side Effects ◽  
Disease Progression ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Metastatic Progression ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Patient Counselling ◽  
Castration Resistant

Docetaxel is the guideline-recommended first-line chemotherapy in men with castration-resistant prostate cancer (CRPC). Despite its proven survival benefit, however, all patients will experience disease progression after a mean interval of six to eight months. Recently, the US Food and Drug Administration approved cabazitaxel and abiraterone acetate as effective second-line treatment options in this clinical scenario. Compared with mitoxantrone, cabazitaxel improves progression-free survival, overall survival, time to prostate surface antigen (PSA) progression, and time to metastatic progression. On the other hand, cabazitaxel is associated with a significantly higher frequency of grade 3/4 hematotoxic and gastrointestinal side effects than mitoxantrone. In experienced hands, and with the use of proactive therapeutic measures (weekly monitoring, adequate patient counselling, appropriate application of the guidelines on management and prophylaxis of neutropenia and diarrhea), all side effects can be handled easily without harming the patient, as has been shown recently by the analysis of the results of the German and European compassionate use programs. Cabazitaxel is one of the key components in the management of disease progression after docetaxel, and might be of benefit in men with high metastatic burden, rapid PSA doubling time, and minimal side effects during first-line docetaxel therapy.

scholarly journals Piperlongumine inhibits migration and proliferation of castration-resistant prostate cancer cells via triggering persistent DNA damage

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ding-fang Zhang ◽  
Zhi-chun Yang ◽  
Jian-qiang Chen ◽  
Xiang-xiang Jin ◽  
Yin-da Qiu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cell Adhesion ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Dna Damage And Repair ◽  
Castration Resistant

Abstract Background Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer. Piperlongumine (PL) is a novel potential anticancer agent that has been demonstrated to exhibit anticancer efficacy against prostate cancer cells. However, the effects of PL on DNA damage and repair against CRPC have remained unclear. The aim of this study was to further explore the anticancer activity and mechanisms of action of PL against CRPC in terms of DNA damage and repair processes. Methods The effect of PL on CRPC was evaluated by MTT assay, long-term cell proliferation, reactive oxygen species assay, western blot assay, flow cytometry assay (annexin V/PI staining), β-gal staining assay and DAPI staining assay. The capacity of PL to inhibit the invasion and migration of CRPC cells was assessed by scratch-wound assay, cell adhesion assay, transwell assay and immunofluorescence (IF) assay. The effect of PL on DNA damage and repair was determined via IF assay and comet assay. Results The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells through affecting the expression and distribution of focal adhesion kinase (FAK), leading to concentration-dependent inhibition of CRPC cell proliferation and concomitantly increased cell death. Moreover, PL treatment triggered persistent DNA damage and provoked strong DNA damage responses in CRPC cells. Conclusion Collectively, our findings demonstrate that PL potently inhibited proliferation, migration, and invasion of CRPC cells and that these potent anticancer effects were potentially achieved via triggering persistent DNA damage in CRPC cells.

scholarly journals Sortilin Regulates Progranulin Action in Castration-Resistant Prostate Cancer Cells

Endocrinology ◽  
2015 ◽  
Vol 156 (1) ◽  
pp. 58-70 ◽  
Author(s):  
Ryuta Tanimoto ◽  
Alaide Morcavallo ◽  
Mario Terracciano ◽  
Shi-Qiong Xu ◽  
Manuela Stefanello ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Castration Resistant

Mental health care utilization among veterans with castration-resistant prostate cancer receiving abiraterone or enzalutamide.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18680-e18680
Author(s):  
Phoebe A. Tsao ◽  
Jennifer A. Burns ◽  
Shami Entenman ◽  
Kyle Kumbier ◽  
Jordan Sparks ◽  
...  
Keyword(s):  
Mental Health ◽  
Prostate Cancer ◽  
Health Care ◽  
Mental Health Care ◽  
Health Administration ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Diagnostic Characteristics ◽  
Comorbidity Burden

e18680 Background: Abiraterone and enzalutamide are oral therapies widely used to treat men with castration-resistant prostate cancer (CRPC). Recent data have suggested potentially worsened quality of life and depression with use of enzalutamide compared to abiraterone. Because Veterans are at a higher risk for mental health conditions, we sought to compare mental health service utilization in Veterans with CRPC receiving enzalutamide to those receiving abiraterone. Methods: The Veterans Health Administration Corporate Data Warehouse was used to identify men with CRPC who received abiraterone or enzalutamide for ≥ 30 days as first-line treatment between 2010-2017. We compared the rate of mental health visits per 100 patient-months for men on abiraterone versus enzalutamide using an exact rate ratio test, assuming Poisson counts. Results: Among 2902 male Veterans, 68.6% (n=1992) received abiraterone and 31.4% (n=910) enzalutamide as first-line therapy. Men who received enzalutamide were older (76 vs 74, p<0.01) and had a higher comorbidity burden (Charlson Comorbidity Index [CCI] ≥ 2 in 28.7% vs 21.6%, p<0.01); no differences were noted in race or prevalence of preexisting documented mental health diagnoses. Median time on drug was 8 months for both medications. There was no difference in the rate of mental health visits per 100 patients-months on enzalutamide versus abiraterone (6.6 v. 6.7, p=0.66). However, within patient sub-groups, men who were age 75 or older, not married, or without notable comorbidities had lower rates of mental health visits with enzalutamide compared to abiraterone; whereas those who were younger than 75, married, had higher comorbidities, or a preexisting mental health diagnosis had higher rates of mental health visits with enzalutamide (Table). Conclusions: Among Veterans with CRPC who received a novel antiandrogen therapy first-line, there was no difference in engagement in mental health care between those who received abiraterone versus enzalutamide. Sub-group analysis revealed significant differences between patients on the two medications in demographic and diagnostic characteristics associated with number of visits, suggesting that vulnerability for mental health symptoms may vary by medication type. Further work in understanding the long-term impact of novel antiandrogens on mental health is needed.[Table: see text]

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