scholarly journals Comparison of Prostate-Specific Promoters and the Use of PSP-Driven Virotherapy for Prostate Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Yi Lu ◽  
Yu Zhang ◽  
Guimin Chang ◽  
Jun Zhang
Keyword(s):  
Prostate Cancer ◽  
Tumor Model ◽  
Canine Model ◽  
Oncolytic Viruses ◽  
Mice Model ◽  
Promising Strategy ◽  
Mmtv Ltr ◽  
Self Replication

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men today. Although virus-based gene therapy is a promising strategy to combat advanced prostate cancer, its current effectiveness is limited partially due to inefficient cellular transductionin vivo. To overcome this obstacle, conditional oncolytic viruses (such as conditional replication adenovirus (CRAD)) are developed to specifically target prostate without (or with minimal) systemic toxicity due to viral self-replication. In this study, we have analyzed and compared three prostate-specific promoters (PSA, probasin, and MMTV LTR) for their specificity and activity bothin vitroandin vivo. Both mice model with xenograft prostate tumor model and canine model were used. The best PSP was selected to construct a prostate-specific oncolytic adenovirus (CRAD) by controlling the adenoviral E1 region. The efficacy and specificity of CRAD on prostate cancer cells were examined in cell culture and animal models.

scholarly journals PSMA-Targeting Redox Hyperbranched Poly (Amido Amine)-Mediated miR-133a-3p Delivery to Inhibit Bone Metastasis of Prostate Cancer

2020 ◽  
Author(s):  
Yongheng Ye ◽  
Lingli Zhang ◽  
Yuhu Dai ◽  
Zhi Wang ◽  
Cuie Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Therapeutic Potential ◽  
Tumor Model ◽  
Lncap Cells ◽  
Systemic Delivery ◽  
Formidable Challenge ◽  
Hyperbranched Poly

Abstract Treatment of bone metastasis of prostate cancer remains a formidable challenge. The skeleton has a poorer blood supply, leading to inadequate drug distribution into the bone after administration. This study aimed to develop aptamer-anchored hyperbranched poly (amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro. A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with miRNA-133a-3p through electrostatic adsorption. The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of miRNA-133a-3p into LNCaP cells was proven, and HPAA-PEG-APT/miRNA-133a-3p demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a mouse tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/miRNA-133a-3p complex significantly inhibited cancer growth and extended the survival time. In summary, this study provided an aptamer-anchored HPAA-loaded gene system to deliver miRNA-133a-3p for better therapeutic efficacy of bone metastasis of prostate cancer.

scholarly journals ID:3005 Combination of vaccine-strain measles and mumps viruses enhances oncolytic activity against human solid malignancies: special focus on prostate cancer

2017 ◽  
Vol 4 (S) ◽  
pp. 17
Author(s):  
Toan Linh Nguyen ◽  
Ho Anh Son ◽  
LiFeng Zhang ◽  
Bui Khac Cuong ◽  
Hoang Van Tong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Therapeutic Option ◽  
Oncolytic Viruses ◽  
Special Focus ◽  
Immunogenic Cell Death ◽  
Solid Malignancies ◽  
Anti Tumor Activity

Oncolytic viruses (OLVs) including measles and mumps viruses (MeV and MuV) have a potential to serve as a therapeutic option for cancers. We have previously shown that the combination of MeV and MuV synergistically kills various human haematological cancer cells. This study aims to investigate the anti-tumor activity of MeV, MuV and MeV-MuV combination (MM) against human solid malignancies in vitro and in vivo. The results showed that MeV, MuV and MM combination targeted and effectively killed various cancer cell lines of human solid malignancies but not normal cells. Notably, MM combination demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer (PC3) xenograft tumour model compared to MeV and MuV. MeV, MuV and MM combination significantly induced the expression of immunogenic cell death (ICD) markers and enhanced spleen-infiltrating immune cells such as macrophages, natural killer and dendritic cells. Our study demonstrated that MM combination is a promising option for treatment of human solid malignancies and suggested that MM could induce immunogenic cell death of malignant cells and activate immunity against cancers.

scholarly journals TRIM59 is Suppressed by Androgen Receptor and Acts to Promote Lineage Plasticity and Neuroendocrine Differentiation in Prostate Cancer

2021 ◽  
Author(s):  
Liancheng Fan ◽  
Yiming Gong ◽  
Yuman He ◽  
Wei-Qiang Gao ◽  
Baijun Dong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Molecular Mechanisms ◽  
Neuroendocrine Differentiation ◽  
Tumor Model ◽  
Strongly Correlated ◽  
Neuroendocrine Prostate Cancer ◽  
In Vitro Effects

Abstract Background: The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of second-generation androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood. Methods: TRIM59 expression was evaluated in PCa samples from patients at first diagnosis or at relapse stage post ARPI treatment by immunohistochemistry; in vitro effects of TRIM59 were determined by cell proliferation, sphere formation and cell migration assays; while in vivo analysis was performed using subcutaneous tumor model. Western blot, qPCR assay, dual luciferase assessment, chromatin immunoprecipitation and RNA sequencing were applied for mechanistic exploration.Results: Here we report that upregulation of TRIM59, a TRIM family protein, is strongly correlated with ARPI treatment mediated NED and shorter patient survival in PCas. AR binds to TRIM59 promoter and represses its transcription. ARPI treatment leads to a reversal of repressive epigenetic modifications on TRIM59 gene and the transcriptional restraint on TRIM59 by AR. Upregulated TRIM59 then drives the NED of PCa by enhancing the degradation of RB1 and P53 and upregulating downstream lineage plasticity-promoting transcription factor SOX2. Conclusion: Altogether, TRIM59 is negatively regulated by AR and acts as a key driver for NED in PCas. Our study provides a novel prognostic marker for PCas and shed new light on the molecular pathogenesis of t-NEPC, a deadly variant of PCa.

1104: In Vitro and In Vivo Assessment of 18F-FLT as a Proliferation Marker in Prostate Cancer Tumor Model

2004 ◽  
Vol 171 (4S) ◽  
pp. 291-291
Author(s):  
Nobuyuki Oyama ◽  
Datta E. Ponde ◽  
Ryuji Higashikubo ◽  
Carmen S. Dence ◽  
Yuan-Chuan Tai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Model ◽  
Proliferation Marker ◽  
Cancer Tumor ◽  
In Vivo Assessment

AVIDIO as a novel oncolytic immunotherapy platform for the treatment of colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15210-e15210
Author(s):  
Bijan Almassian ◽  
Bhaskara R Madina ◽  
Ju Chen ◽  
Xiaoyang Ye ◽  
Marie M Krady ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Tumor Growth ◽  
Semliki Forest Virus ◽  
Tumor Model ◽  
Oncolytic Viruses ◽  
Immunomodulatory Agents ◽  
Oncolytic Activity

e15210 Background: Colorectal cancer is the third deadliest of all cancers causing more than 50,000 deaths per year in the U.S. Oncolytic viruses have seen limited use for the treatment of cancers, and further improvement of these methods with immune-modulating activities may prove crucial for the effectiveness of these agents in the treatment of human malignancies. To this end, we developed an artificial virus for infectious diseases and immuno-oncology (AVIDIO) platform that employs virus-like vesicles (VLV) for both the delivery of immunomodulatory agents to tumors and oncolytic activity. Methods: The AVIDIO platform is comprised of in vitro evolved RNA-dependent RNA polymerase from an alphavirus, Semliki forest virus, and envelope glycoproteins from vesicular stomatitis virus, which together form VLVs. Both unarmed VLVs and VLVs armed with the p35 subunit of IL-12 (VLV-IL12p35), an immunomodulatory cytokine that can induce Th1-mediated immunity, were tested for oncolytic activity against various cancer cell lines, including MC38 colorectal cancer cells, in vitro. Using the MC38 syngeneic murine tumor model, we evaluated the antitumor activity of VLV-IL-12p35 in vivo. We used tumor growth measurements and analyses of tumor-infiltrating cells after consecutive treatments with VLV-IL-12p35 to monitor its antitumor and immunomodulatory activities, respectively. Results: VLV-IL-12p35 showed robust oncolytic activity against MC38 cells in vitro, killing over 80% of cells within 24 h. Treatment of intradermal MC38 tumors by intra-tumoral delivery of VLV-IL-12p35 resulted in more than 65% suppression of tumor growth within 2 weeks ( p< 0.05). VLV-IL-12p35-treated tumors also harbored significantly more CD8+ T cells, IFN-gamma-producing CD4+ T cells, and reduced numbers of Foxp3+ regulatory T cells. Conclusions: Our results show that VLV-IL-12p35 derived from the AVIDIO platform has oncolytic activity in vitro and antitumor and immunomodulatory activities in vivo. Therefore, AVIDIO is a promising platform for the delivery of immunomodulatory agents to tumors. Further optimization of the platform, including the addition of other immunomodulatory agents, is in progress to advance the AVIDIO platform to clinical applications for colorectal cancer.

scholarly journals Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12–IFN-γ

2017 ◽  
Vol 114 (43) ◽  
pp. 11482-11487 ◽  
Author(s):  
Madhuchhanda Kundu ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Cancer ◽  
Critical Role ◽  
Tumor Model ◽  
Cell Mediated Immunity ◽  
Ifn Γ

Cancer cells are adept at evading cell death, but the underlying mechanisms are poorly understood. IL-12 plays a critical role in the early inflammatory response to infection and in the generation of T-helper type 1 cells, favoring cell-mediated immunity. IL-12 is composed of two different subunits, p40 and p35. This study underlines the importance of IL-12 p40 monomer (p40) in helping cancer cells to escape cell death. We found that different mouse and human cancer cells produced greater levels of p40 than p40 homodimer (p402), IL-12, or IL-23. Similarly, the serum level of p40 was much greater in patients with prostate cancer than in healthy control subjects. Selective neutralization of p40, but not p402, by mAb stimulated death in different cancer cells in vitro and in vivo in a tumor model. Interestingly, p40 was involved in the arrest of IL-12 receptor (IL-12R) IL-12Rβ1, but not IL-12Rβ2, in the membrane, and that p40 neutralization induced the internalization of IL-12Rβ1 via caveolin and caused cancer cell death via the IL-12–IFN-γ pathway. These studies identify a role of p40 monomer in helping cancer cells to escape cell death via suppression of IL-12Rβ1 internalization.

scholarly journals Regression of Castration-Resistant Prostate Cancer by a Novel Compound HG122

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaonan Cong ◽  
Yundong He ◽  
Haigang Wu ◽  
Dingxiang Wang ◽  
Yongrui Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Target Genes ◽  
Mrna Level ◽  
Tumor Model ◽  
Life Cycle Management ◽  
Potential Candidate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Prostate cancer (PCa) is a common aggressive disease worldwide which usually progresses into incurable castration-resistant prostate cancer (CRPC) in most cases after 18–24 months treatment. Androgen receptor (AR) has been considered as a crucial factor involved in CRPC and the study of AR as a potential therapeutic target in CRPC may be helpful in disease control and life-cycle management. In this study, we identified a potent small molecule compound, HG122, that suppressed CRPC cells proliferation and metastasis, and inhibited tumor growth both in subcutaneous and orthotopic tumor model. In addition, HG122 reduced the mRNA expression of PSA and TMPRSS2 which are target genes of AR, resulting in cell growth inhibition and metastasis suppression of CRPC, without affecting the expression of AR mRNA level. Mechanically, HG122 promoted AR protein degradation through the proteasome pathway impairing the AR signaling pathway. In conclusion, HG122 overcomes enzalutamide (ENZ) resistance in CRPC both in vitro and in vivo, thus suggesting HG122 is a potential candidate for the clinical prevention and treatment of CRPC.

Oncolytic HSV and PI3K inhibitor BKM120 synergize to promote killing of prostate cancer stem-like cells.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16503-e16503
Author(s):  
Lei Wang
Keyword(s):  
Prostate Cancer ◽  
Tumor Model ◽  
Complete Regression ◽  
Novel Therapies ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
Anti Tumor Activity

e16503 Background: Novel therapies to override chemo-radiation resistance in prostate cancer (PCa) are needed. Prostate cancer sphere-forming cells (PCSCs) (also termed prostate cancer stem-like cells) likely participate in tumor progression and recurrence and are important therapeutic targets. Methods: We established PCSC-enriched spheres by culturing human (DU145) and murine (TRAMP-C2) PCa cells in growth factor-defined serum-free medium, and characterized stem-like properties of clonogenicity and tumorigenicity in vivo. The efficacy of two different oHSVs (G47∆ and MG18L) in PCSCs was tested alone and in combination with radiation, chemotherapy, and inhibitors of PI3K, Wnt, and NOTCH in vitro, and G47∆ with BKM120 in a PCSC-derived tumor model in vivo. Results: PCSCs were more tumorigenic than serum-cultured parental cells. Human and murine PCSCs were sensitive to oHSV and BKM120 killing in vitro, while the combination was synergistic. In contrast, oHSV combined with radiation, docetaxel, Wnt, or NOTCH inhibitors was not. In athymic mice bearing DU145 PCSC-derived tumors, combination intra-tumoral G47∆ and systemic BKM120 induced complete regression of tumors in 2 of 7 animals, and exhibited superior anti-tumor activity compared to either monotherapy alone, with no detectable toxicity. Conclusions: oHSV synergizes with BKM120 in killing PCSCs in vitro and the combination markedly inhibits tumor growth even inducing regression in vivo.

scholarly journals Anti-tumor potential of cucurbitacin triterpenoids of Momordica dioica Roxb. fruit by EAC induced ascites tumor model

2020 ◽  
Vol 11 (2) ◽  
pp. 1793-1797
Author(s):  
Madesh T ◽  
Abhinav Raj Ghosh ◽  
Krishna K L ◽  
Seema Mehdi ◽  
Nandini H S ◽  
...  
Keyword(s):  
Body Weight ◽  
Life Span ◽  
Hematological Parameters ◽  
Tumor Model ◽  
In Vivo Studies ◽  
Percentage Increase ◽  
Mice Model ◽  
Anticancer Efficacy

Momordica dioicaRoxb. (Cucurbitaceae) is commonly known as spiny gourd and traditionally used as astringent, febrifuge, antiseptic, anthelmintic, spermicidal and also used in bleeding piles, urinary infection and as a sedative. Studies indicate that it possesses antioxidant, hepatoprotective, antibacterial, anti-inflammatory, anti-lipid peroxidative, hypoglycaemic and analgesic properties. In this study, the anticancer efficacy of Cucurbitacins obtained from Momordica dioicaRoxb. (MDR) has been evaluated. Based on previous in-vitro studies performed, in-vivo studies were carried out on mice model.  Ehrlich ascites carcinoma (EAC) cells were inoculated into swiss albino mice intraperitoneally to form a liquid tumor and then treated with oral administration of 50, 100, 200mg/kg. Evaluation parameters involved the mean survival time (MST), body weight, hematological parameters, Percentage increase in life span were measured in normal control, EAC control and Cucurbitacintreated groups (n = 6). Treatment with Cucurbitacins enriched fraction has shown anti-tumor effects against liquid tumor as indicated by a significant (P < 0.05) reduction in body weight. Interestingly, the enriched bio fraction restored the altered hematological parameters of tumor-bearing animals and significantly increased their life span. These data indicate the cytotoxic potential effects of MDRon tumor cells opening new opportunities for further studies on the anti-cancer effects of this agent.

scholarly journals Radiosensitizing Effect of Bromelain Using Tumor Mice Model via Ki-67 and PARP-1 Inhibition

2021 ◽  
Vol 20 ◽  
pp. 153473542110603
Author(s):  
Mai H. Mekkawy ◽  
Hanan A. Fahmy ◽  
Ahmed S. Nada ◽  
Ola S. Ali
Keyword(s):  
Tumor Cells ◽  
Tumor Model ◽  
Mouse Tumor ◽  
Mice Model ◽  
Ki 67 ◽  
Radiosensitizing Effect ◽  
Treatment And Prevention ◽  
Parp 1

Recent reports have shown that bromelain (BL), a pineapple extract, acts as an adjuvant therapy in cancer treatment and prevention of carcinogenesis. The present study was designed to investigate the possible mechanisms by which BL could radiosensitize tumor cells in vitro and in a mouse tumor model. BL has shown a significant reduction in the viability of the radioresistant human breast carcinoma (MCF-7) cell line using cell proliferation assay. The in vivo study was designed using the Ehrlich model in female albino mice, treated with BL (6 mg/kg b. wt., intraperitoneal, once daily for 10 days) 1 hour before exposure to a fractionated dose of gamma radiation (5 Gy, 1 Gy for 5 subsequent days). The radiosensitizing effect of BL was evident in terms of a significant reduction in tumor volume, poly ADP ribose polymerase-1 (PARP-1), the proliferation marker Ki-67 and nuclear factor kappa activated B cells (NF-κB) with a significant elevation in the reactive oxygen species (ROS) content and lipid peroxidation (LPO) in tumor cells. The present findings offer a novel insight into the radiosensitizing effect of BL and its potential application in the radiotherapy course.

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