Short-term clinicopathological outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade, followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with high-risk localized prostate cancer

Narita, Shintaro; Tsuchiya, Norihiko; Kumazawa, Teruaki; Maita, Shinya; Numakura, Kazuyuki; Obara, Takashi; Takahashi, Hiroshi; Saito, Mitsuru; Inoue, Takamitsu; Horikawa, Yohei; Satoh, Shigeru; Nanjyo, Hiroshi; Habuchi, Tomonori

doi:10.1186/1477-7819-10-1

Cited by 81 publications

(51 citation statements)

References 18 publications

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“…Meanwhile, mitochondrial apoptotic pathway was also activated by RBM5 as caspase-9 and caspase-3 activity was upregulated greatly. In another study, expression of cleaved caspase-9 and cleaved caspase-3 was upregulated by RBM5 in prostate cancer [10]. In this study, we demonstrated that Bcl-2 was downregulated while the level of Bax, cleaved caspase-3, and TNF-α was increased significantly by RBM5 in gliomas cells, which suggest that RBM5, at least partly, promoted cell apoptosis in gliomas cells.…”

Section: Discussionsupporting

confidence: 65%

“…Moreover, RBM5 was evaluated as a therapeutic and diagnostic marker in lung cancer [9]. Overexpression of RBM5 inhibited growth of human prostate cancer while it was demonstrated to be downregulated in serous ovarian carcinoma [10, 11]. In fact, accumulating data suggest that RBM5 was a tumor suppressor and inhibited tumor growth or progression by triggering apoptosis and inducing cell cycle G1/S arrest [12].…”

Section: Introductionmentioning

confidence: 99%

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RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/β-catenin signaling and induction of apoptosis

et al. 2017

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BackgroundGliomas are one of the most common malignant brain tumors and bring a big threat to human life as traditional therapy is unsatisfactory. RBM5 was a RNA-binding motif protein and was reported as a tumor suppressor. But the role of RBM5 in gliomas was unknown.MethodsThe mRNA level of RBM5 was determined in gliomas tissues and cell lines by real-time quantitative PCR (qRT-PCR) assay while the association of RBM5 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. Lentivirus was used to overexpress RBM5 in gliomas cells. MTT and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis when the ability of cell migration and invasion was analyzed by transwell assay with/without Matrigel. Cell apoptosis rate was determined with fluorescence-activated cell sorting (FACS) method. Then, expression of apoptosis molecules and critical members in Wnt/β-catenin pathway were detected by western blot analysis.ResultsRBM5 was shown to be downregulated in gliomas tissues and gliomas cell lines. And decreased RBM5 expression was clinically correlated with tumor stage, patient age, and poor prognosis of gliomas patients. The proliferation and DNA synthesis was dramatically inhibited when RBM5 was overexpressed in SHG44 or U251 cells. Also, the ability of cell migration and invasion was disrupted. Then, the level of β-catenin and Cyclin D1 significantly decreased when DKK1 and P-GSK-3β increased reversely in SHG44 cells, which suggested that RBM5 inhibited canonical Wnt/β-catenin signaling. Meanwhile, we demonstrated that caspase3-mediated apoptotic pathway was activated by RBM5 as Bax, TNF-α, and cleaved caspase3 were greatly upregulated while antiapoptotic molecule Bcl-2 was downregulated. Additionally, that apoptotic rate increased significantly from less than 1 to 32% in RBM5-overexpressed SHG44 cells further supported the pro-apoptosis role of RBM5 in gliomas cells.ConclusionsRBM5 plays a suppressor role in human gliomas by inhibiting Wnt/β-catenin signaling and inducing cell apoptosis. This study improves our knowledge about the carcinogenesis and progression of human gliomas, which would greatly contribute to the therapy for gliomas patients.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/β-catenin signaling and induction of apoptosis

et al. 2017

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“…Recurrent disease due to micrometastases that escape exposure to therapeutics is a major driver of patient mortality. Designing strategies that allow drugs to reach micrometastatic sites and the tumor microenvironment is therefore imperative (43,44). In this work, we developed a targeted α-particle platform that we demonstrated can target GBM with lethal α-particles and simultaneously enhance BBB and BTB permeability towards systemically administered agents.…”

Section: Discussionmentioning

confidence: 99%

Alpha Particle Enhanced Blood Brain/Tumor Barrier Permeabilization in Glioblastomas Using Integrin Alpha-v Beta-3–Targeted Liposomes

Sattiraju

Xiong

Pandya

et al. 2017

Molecular Cancer Therapeutics

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Glioblastoma (GBM) is the most common primary malignant astrocytoma characterized by extensive invasion, angiogenesis, hypoxia and micrometastasis. Despite the relatively leaky nature of GBM blood vessels, effective delivery of anti-tumor therapeutics has been a major challenge due to the complications caused by the blood brain barrier (BBB) and the highly torturous nature of newly formed tumor vasculature (blood tumor barrier-BTB). External beam radiation therapy was previously shown to be an effective means of permeabilizing central nervous system (CNS) barriers. By using targeted short ranged radionuclides, we show for the first time that our targeted actinium-225 labeled αvβ3-specific liposomes (225Ac-IA-TLs) caused catastrophic double stranded DNA breaks and significantly enhanced the permeability of BBB and BTB in mice bearing orthotopic GBMs. Histological studies revealed characteristic α-particle induced double strand breaks within tumors but was not significantly present in normal brain regions away from the tumor where BBB permeability was observed. These findings indicate that the enhanced vascular permeability in these distal regions did not result from direct α-particle induced DNA damage. Based on these results, in addition to their direct anti-tumor effects, 225Ac-IA-TLs can potentially be used to enhance the permeability of BBB and BTB for effective delivery of systemically administered anti-tumor therapeutics.

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“…Several clinical trials have been conducted recently exploring the potential of neoadjuvant chemotherapy in patients with high-risk localised prostate cancer (Womble et al , 2011; Narita et al , 2012; Ross et al , 2012). The results of these trials suggest a benefit to patients in terms of reductions in tumour volume and PSA levels (Womble et al , 2011; Ross et al , 2012).…”

Section: Discussionmentioning

confidence: 99%

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

Toner

McLaughlin²,

Giles

et al. 2013

Br J Cancer

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Background:Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer.Methods:The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background.Results:EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102.Conclusion:EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.

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Short-term clinicopathological outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade, followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with high-risk localized prostate cancer

Cited by 81 publications

References 18 publications

RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/β-catenin signaling and induction of apoptosis

RBM5 inhibits tumorigenesis of gliomas through inhibition of Wnt/β-catenin signaling and induction of apoptosis

Alpha Particle Enhanced Blood Brain/Tumor Barrier Permeabilization in Glioblastomas Using Integrin Alpha-v Beta-3–Targeted Liposomes

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance

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