scholarly journals Establishment of An Orthotopic Prostate Cancer Xenograft Mouse Model Using Microscope-Guided Orthotopic Injection of LNCaP Cells Into The Dorsal Lobe of The Mouse Prostate

2021 ◽  
Author(s):  
Weiyong Liu ◽  
Yunkai Zhu ◽  
Lei Ye ◽  
Yajuan Zhu ◽  
Yuhao Wang
Keyword(s):  
Prostate Cancer ◽  
Mouse Model ◽  
Ultrasound Imaging ◽  
Athymic Nude Mouse ◽  
Lncap Cells ◽  
Nude Mouse Model ◽  
Prostate Tumorigenesis ◽  
Mouse Prostate ◽  
The Individual

Abstract Background: Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; however, orthotopic injection of LNCaP cells into the mouse prostate remains a challenge.Methods: Under the guidance of a stereoscopic microscope, the anatomy of the individual prostate lobes in male Balb/c athymic nude mice was investigated, and LNCaP cells were inoculated into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans. Real-time ultrasound imaging was used to monitor orthotopic prostate tumorigenesis, contrast-enhanced ultrasonography (CEUS) was used to characterize tumor angiogenesis, and macroscopic and microscopic characteristics of tumors were described.Results: The DP had a trigonal bipyramid-shape and were located at the base of the seminal vesicles. After orthotopic inoculation, gray scale ultrasound imaging showed progressive changes in tumor echotexture, shape and location, and tumors tended to protrude into the bladder. After 8 weeks, the tumor take rate was 65% (n= 13/20 mice). On CEUS, signal intensity increased rapidly, peaked, and decreased gradually. Observations of gross specimens showed orthotopic prostate tumors were well circumscribed, round, dark brown, and soft, with a smooth outer surface and a glossy appearance. Microscopically, tumor cells were arranged in acini encircled by fibrous septa with variably thickened walls, mimicking human adenocarcinoma.Conclusions: This study describes a successful approach to establishing an orthotopic LNCaP xenograft Balb/c athymic nude mouse model. The model requires a thorough understanding of mouse prostate anatomy and proper technique. The model represents a valuable tool for the in vivo study of the biological processes involved in angiogenesis in prostate cancer and preclinical evaluations of novel anti-angiogenic therapies.

scholarly journals Prostate Cancer Metastases Are Strongly Inhibited by Agonistic Epha2 Ligands in an Orthotopic Mouse Model

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2854
Author(s):  
Ahmed F. Salem ◽  
Luca Gambini ◽  
Sandrine Billet ◽  
Yu Sun ◽  
Hiromichi Oshiro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Mouse Model ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Tyrosine Kinase Receptor ◽  
Nude Mouse Model ◽  
Orthotopic Mouse Model

The EphA2 tyrosine kinase receptor is highly expressed in several types of solid tumors. In our recent studies, we targeted EphA2 in pancreatic cancer with agonistic agents and demonstrated that suppression of EphA2 significantly reduced cancer-cell migration in cell-based assays. In the present study, we focused on targeting EphA2 in prostate cancer. While not all prostate cancers express EphA2, we showed that enzalutamide induced EphA2 expression in prostate cancer cells and in a patient-derived xenograft (PDX) animal model, which provides further impetus to target EphA2 in prostate cancer. Western blot studies showed that agonistic dimeric synthetic (135H12) and natural (ephrinA1-Fc) ligands effectively degraded EphA2 receptor in the prostate cancer cell line PC-3. The agents also delayed cell migration of prostate cancer (PC-3) cells, while an in vivo PC-3 orthotopic metastatic nude-mouse model also revealed that administration of ephrinA1-Fc or 135H12 strongly reduced metastases. The present study further validates EphA2 as an important target in metastatic prostate cancer treatment. Our results should incentivize further efforts aimed at developing potent and effective EphA2 synthetic agonistic agents for the treatment of EphA2-driven aggressive metastatic tumors including prostate, pancreatic, and breast cancer.

scholarly journals Endocytic Adaptor Protein Epsin Is Elevated in Prostate Cancer and Required for Cancer Progression

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kandice L. Tessneer ◽  
Satish Pasula ◽  
Xiaofeng Cai ◽  
Yunzhou Dong ◽  
Xiaolei Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Potential Role ◽  
Adaptor Protein ◽  
Wild Type ◽  
Prostate Cancer Cells ◽  
Prostate Tumorigenesis ◽  
Tramp Mouse ◽  
Mouse Prostate

Epsins have an important role in mediating clathrin-mediated endocytosis of ubiquitinated cell surface receptors. The potential role for epsins in tumorigenesis and cancer metastasis by regulating intracellular signaling pathways has largely not been explored. Epsins are reportedly upregulated in several types of cancer including human skin, lung, and canine mammary cancers. However, whether their expression is elevated in prostate cancer is unknown. In this study, we investigated the potential role of epsins in prostate tumorigenesis using the wild type or epsin-deficient human prostate cancer cells, LNCaP, in a human xenograft model, and the spontaneous TRAMP mouse model in wild type or epsin-deficient background. Here, we reported that the expression of epsins 1 and 2 is upregulated in both human and mouse prostate cancer cells and cancerous tissues. Consistent with upregulation of epsins in prostate tumors, we discovered that depletion of epsins impaired tumor growth in both the human LNCaP xenograft and the TRAMP mouse prostate. Furthermore, epsin depletion significantly prolonged survival in the TRAMP mouse model. In summary, our findings suggest that epsins may act as oncogenic proteins to promote prostate tumorigenesis and that depletion or inhibition of epsins may provide a novel therapeutic target for future prostate cancer therapies.

A Nude Mouse Model as an in vivo Infectivity Assay for Cryptospomdiosis

1993 ◽  
Vol 27 (3-4) ◽  
pp. 65-68 ◽  
Author(s):  
B. H. Kwa ◽  
M. Moyad ◽  
M. A. Pentella ◽  
J. B. Rose
Keyword(s):  
Drinking Water ◽  
Mouse Model ◽  
Nude Mouse ◽  
Cryptosporidium Parvum ◽  
Nude Mice ◽  
Surface Waters ◽  
Nude Mouse Model ◽  
Infectivity Assay ◽  
Limiting Dilution

Cryptosporidium parvum is an important patliogen of diarrlieal disease which has been implicated in several outbreaks associated with contamination of surface waters. In monitoring for C. parvum in drinking water sources, it is important to asce tain the viability, and more importantly, the infectivity of low numbers of recovered oocysts. Groups of 10 Balb/C nude (nu/nu) mice, 4-8 weeks old at time of inoculation, were infected with C. parvum oocysts from naturally infected calves and purified using Sheather's sucrose gradients. Oocysts were counted using the Merifluor IFA kit (Meridian). Each group of 10 mice were infected with 1,10,100 and 1000 oocysts respectively. Numbers of oocysts per inoculation were determined by limiting dilution, and parallel inocula were counted microscopically to ascertain the accuracy of the dilutions. Two uninfected nude mice were kept in each cage to serve as controls. Mouse stools were collected every 4 days, concentrated using the Fekal Kontrate Concentration Kit (Meridian) and oocysts were counted with a UV microscope using the Merifluor IFA Kit (Meridian). Oocyst counts were expressed in terms of number of oocyst/g feces. Mice inoculated with 1000 oocysts began to shed oocysts on day 32, mice inoculated with 100 oocysts began to shed on days 44-48, mice inoculated with 10 oocysts began to shed on days 56-60, and mice inoculated with 1 oocyst shed on days 68-88. All infected mice continued to shed oocysts intermittently and with variable oocyst counts until day 180 when the experiment was terminated. This study established that it is possible to infect nude mice with very low numbers, down to a single oocyst. We are currently in the process of correlating the nude mouse assay with other viability assays.

scholarly journals Molecular imaging of orthotopic prostate cancer with nanobubble ultrasound contrast agents targeted to PSMA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Wang ◽  
Al Christopher De Leon ◽  
Reshani Perera ◽  
Eric Abenojar ◽  
Ramamurthy Gopalakrishnan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ultrasound Imaging ◽  
Prostate Gland ◽  
Ultrasound Contrast Agent ◽  
Tumor Model ◽  
Focal Therapy ◽  
Ultrasound Contrast Agents ◽  
Time Intensity Curve ◽  
Ultrasound Contrast

AbstractUltrasound imaging is routinely used to guide prostate biopsies, yet delineation of tumors within the prostate gland is extremely challenging, even with microbubble (MB) contrast. A more effective ultrasound protocol is needed that can effectively localize malignancies for targeted biopsy or aid in patient selection and treatment planning for organ-sparing focal therapy. This study focused on evaluating the application of a novel nanobubble ultrasound contrast agent targeted to the prostate specific membrane antigen (PSMA-targeted NBs) in ultrasound imaging of prostate cancer (PCa) in vivo using a clinically relevant orthotopic tumor model in nude mice. Our results demonstrated that PSMA-targeted NBs had increased extravasation and retention in PSMA-expressing orthotopic mouse tumors. These processes are reflected in significantly different time intensity curve (TIC) and several kinetic parameters for targeted versus non-targeted NBs or LUMASON MBs. These, may in turn, lead to improved image-based detection and diagnosis of PCa in the future.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

scholarly journals Reversal of the Warburg phenomenon in chemoprevention of prostate cancer by sulforaphane

2019 ◽  
Vol 40 (12) ◽  
pp. 1545-1556 ◽  
Author(s):  
Krishna B Singh ◽  
Eun-Ryeong Hahm ◽  
Joshi J Alumkal ◽  
Lesley M Foley ◽  
T Kevin Hitchens ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lactate Production ◽  
Human Prostate ◽  
Resonance Spectroscopy ◽  
Hexokinase Ii ◽  
Mouse Prostate ◽  
Lactate Levels ◽  
In Cells

Abstract Inhibition of metabolic re-programming represents an attractive approach for prevention of prostate cancer. Studies have implicated increased synthesis of fatty acids or glycolysis in pathogenesis of human prostate cancers. We have shown previously that prostate cancer prevention by sulforaphane (SFN) in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model is associated with inhibition of fatty acid metabolism. This study utilized human prostate cancer cell lines (LNCaP, 22Rv1 and PC-3), two different transgenic mouse models (TRAMP and Hi-Myc) and plasma specimens from a clinical study to explore the glycolysis inhibition potential of SFN. We found that SFN treatment: (i) decreased real-time extracellular acidification rate in LNCaP, but not in PC-3 cell line; (ii) significantly downregulated expression of hexokinase II (HKII), pyruvate kinase M2 and/or lactate dehydrogenase A (LDHA) in vitro in cells and in vivo in neoplastic lesions in the prostate of TRAMP and Hi-Myc mice; and (iii) significantly suppressed glycolysis in prostate of Hi-Myc mice as measured by ex vivo1H magnetic resonance spectroscopy. SFN treatment did not decrease glucose uptake or expression of glucose transporters in cells. Overexpression of c-Myc, but not constitutively active Akt, conferred protection against SFN-mediated downregulation of HKII and LDHA protein expression and suppression of lactate levels. Examination of plasma lactate levels in prostate cancer patients following administration of an SFN-rich broccoli sprout extract failed to show declines in its levels. Additional clinical trials are needed to determine whether SFN treatment can decrease lactate production in human prostate tumors.

Super-resolution ultrasound imaging for in vivo microvasculature assessment in acute kidney injury mouse model

2019 ◽  
Vol 145 (3) ◽  
pp. 1859-1859
Author(s):  
Qiyang Chen ◽  
Brittney M. Rush ◽  
Jaesok Yu ◽  
Roderick Tan ◽  
Kang Kim
Keyword(s):  
Acute Kidney Injury ◽  
Mouse Model ◽  
Ultrasound Imaging ◽  
Kidney Injury ◽  
Super Resolution

scholarly journals Secalonic Acid-F, a Novel Mycotoxin, Represses the Progression of Hepatocellular Carcinoma via MARCH1 Regulation of the PI3K/AKT/β-catenin Signaling Pathway

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 393 ◽  
Author(s):  
Lulu Xie ◽  
Minjing Li ◽  
Desheng Liu ◽  
Xia Wang ◽  
Peiyuan Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Mouse Model ◽  
Colony Formation ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Nude Mouse Model ◽  
Hep3b Cells

Liver cancer is a very common and significant health problem. Therefore, powerful molecular targeting agents are urgently needed. Previously, we demonstrated that secalonic acid-F (SAF) suppresses the growth of hepatocellular carcinoma (HCC) cells (HepG2), but the other anticancer biological functions and the underlying mechanism of SAF on HCC are unknown. In this study, we found that SAF, which was isolated from a fungal strain in our lab identified as Aspergillus aculeatus, could inhibit the progression of hepatocellular carcinoma by targeting MARCH1, which regulates the PI3K/AKT/β-catenin and antiapoptotic Mcl-1/Bcl-2 signaling cascades. First, we confirmed that SAF reduced the proliferation and colony formation of HCC cell lines (HepG2 and Hep3B), promoted cell apoptosis, and inhibited the cell cycle in HepG2 and Hep3B cells in a dose-dependent manner. In addition, the migration and invasion of HepG2 and Hep3B cells treated with SAF were significantly suppressed. Western blot analysis showed that the level of MARCH1 was downregulated by pretreatment with SAF through the regulation of the PI3K/AKT/β-catenin signaling pathways. Moreover, knockdown of MARCH1 by small interfering RNAs (siRNAs) targeting MARCH1 also suppressed the proliferation, colony formation, migration, and invasion as well as increased the apoptotic rate of HepG2 and Hep3B cells. These data confirmed that the downregulation of MARCH1 could inhibit the progression of hepatocellular carcinoma and that the mechanism may be via PI3K/AKT/β-catenin inactivation as well as the downregulation of the antiapoptotic Mcl-1/Bcl-2. In vivo, the downregulation of MARCH1 by treatment with SAF markedly inhibited tumor growth, suggesting that SAF partly blocks MARCH1 and further regulates the PI3K/AKT/β-catenin and antiapoptosis Mcl-1/Bcl-2 signaling cascade in the HCC nude mouse model. Additionally, the apparent diffusion coefficient (ADC) values, derived from magnetic resonance imaging (MRI), were increased in tumors after SAF treatment in a mouse model. Taken together, our findings suggest that MARCH1 is a potential molecular target for HCC treatment and that SAF is a promising agent targeting MARCH1 to treat liver cancer patients.

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