NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells Molecular Bases of Disease
In this study using RNA-Seq and bioinformatics analyses, we observed that NOTCH signaling is a deregulated pathway in enzalutamide-resistant cells. NOTCH2 and c-MYC gene expression positively correlated with AR expression in samples from patient with hormone refractory disease in which AR expression levels correspond to those typically observed in enzalutamide resistance. Cleaved NOTCH1, HES1 (Hes family BHLH transcription factor 1), and c-MYC protein expression levels are elevated in two enzalutamide-resistant cell lines, MR49F and C4-2R, indicating NOTCH signaling activation. Moreover, inhibition of the overexpressed ADAM metallopeptidase domain 10 (ADAM10) in the resistant cells induces an exclusive reduction in cleaved NOTCH1 expression. Furthermore, exposure of enzalutamide-resistant cells to both PF-03084014 and enzalutamide increased cell death, decreased colony formation ability, and resensitized cells to enzalutamide. Knockdown of NOTCH1 in C4-2R increased enzalutamide sensitivity by decreasing cell proliferation and increasing cleaved PARP expression. In a 22RV1 xenograft model, PF-03084014 and enzalutamide decreased tumor growth through reducing cell proliferation and increasing apoptosis. These results indicate that NOTCH1 signaling may contribute to enzalutamide resistance in prostate cancer, and inhibition of NOTCH signaling can resensitize resistant cells to enzalutamide.
This study aims to investigate the apoptotic and anti-angiogenic effect of Zoledronic acid on hormone-refractory prostate cancer cell lines. XTT cell proliferation assay used to assess cytotoxicity. Caspase 3/7 activity and DNA fragmentation were measured to verify apoptosis. Angiogenic cytokine profiles investigated using the human angiogenesis antibody array I. Administration of Zoledronic acid on PC-3 and DU-145 prostate cancer cell lines resulted in increased cytotoxicity and apoptosis with a time- and dose-related manner. Also, the administration of Zoledronic acid significantly reduced several angiogenic cytokine pro...
Authors: Papasotiriou I, Apostolou P, Ntanovasilis DA, Parsonidis P, Osmonov D, Jünemann KP Abstract Hormone-refractory prostate carcinoma has a different cell surface protein profile than hormone-sensitive prostate carcinoma, which provides migration ability and interactions with organs/tissues. Detection and association of these proteins with lymph node metastasis via lymphadenectomy might be beneficial for patients. Gene expression analysis in hormone-refractory and hormone-sensitive commercial cancer cell lines was performed and, after co-cultivation with osteoblasts or endothelial cells, knockdown experim...
Publication date: October 2020Source: Biomedicine &Pharmacotherapy, Volume 130Author(s): Henrique Herbst Rosa, Pamela Carvalho, Caroline Flach Ortmann, Naira Fernanda Zanchett Schneider, Flávio Henrique Reginatto, Cláudia Maria Oliveira Simões, Izabella Thaís Silva
CONCLUSIONS: The results showed the in vitro cytotoxic potential of the triterpene-enriched fraction obtained from the leaves of C. pachystachya on human prostate cancer PC3 cell line. PMID: 32768881 [PubMed - as supplied by publisher]
Brachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy.
Abstract We aimed to estimate the risk of secondary cancer after radiotherapy (RT) in high-risk prostate cancer (HRPC) patients with pelvic irradiation. Computed tomography data of five biopsy-proven HRPC patients were selected for this study. Two different planning target volumes (PTV1 and PTV2 ) were contoured for each patient. The PTV1 included the prostate, seminal vesicles, and pelvic lymphatics, while the PTV2 included only the prostate and seminal vesicles. The prescribed dose was 54 Gy for the PTV1 with a sequential boost (24 Gy for the PTV2 ). Intensity-modulated RT (IMRT) and volumetric modulat...
Conclusion: Our study demonstrated that the TGF-β-acetylated KLF5-Bcl-2 signaling axis mediates DTX resistance in prostate cancer and blockade of this pathway could provide clinical insights into chemoresistance of prostate cancer.
Conclusion: The results of this study may provide helpful evidence of DP for the treatment of patients with HRPC. Systematic review registration: INPLASY202040112.
In this report, we present a typical case of “double-negative” end-stage prostate cancer that morphologically resembled basal cell carcinoma of prostate, basaloid large nest type.
Gautam KumarIndian Journal of Urology 2020 36(2):144-145