PLA-based thermogel for the sustained delivery of chemotherapeutics in a mouse model of hepatocellular carcinoma

RSC Advances ◽  
2016 ◽  
Vol 6 (50) ◽  
pp. 44506-44513 ◽  
Author(s):  
Yun-Long Wu ◽  
Han Wang ◽  
Ying-Kun Qiu ◽  
Xian Jun Loh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mouse Model ◽  
Sustained Delivery ◽  
Anti Cancer ◽  
First Time ◽  
Further Development

This work represents the first time that poly(PEG/PPG/PLA urethane) has been used for the delivery of drugs to tumours in vivo and the encouraging results point to the potential for further development of this thermogel platform for anti-cancer applications.

scholarly journals Combining chloroquine with RAD001 inhibits tumor growth in a NEN mouse model

2018 ◽  
Vol 25 (6) ◽  
pp. 677-686 ◽  
Author(s):  
Shani Avniel-Polak ◽  
Gil Leibowitz ◽  
Victoria Doviner ◽  
David J Gross ◽  
Simona Grozinsky-Glasberg
Keyword(s):  
Mouse Model ◽  
Tumor Growth ◽  
Mtor Inhibitors ◽  
Degradation Pathway ◽  
Neuroendocrine Neoplasms ◽  
Histopathological Analysis ◽  
Anti Cancer ◽  
Subcutaneous Xenograft ◽  
Rheumatic Drug

Patients with neuroendocrine neoplasms (NENs) often require systemic treatment, which is frequently limited by the emergence of drug resistance. mTOR inhibitors (mTORi), such as RAD001 (everolimus), have been shown to inhibit neoplasm progression. mTORi stimulates autophagy, a degradation pathway that might promote the survival of neoplasm cells that are exposed to anti-cancer therapy. Chloroquine (CQ), a well-known anti-malarial and anti-rheumatic drug, suppresses autophagy. Based on our previous results, we hypothesized that CQ may enhance the anti-tumorigenic effects of mTORi by inhibiting autophagy and we aimed to examine the anti-tumorigenic effect of CQ, alone or in combination with RAD001. We established a NEN subcutaneous xenograft mouse model and evaluated the effect of the drugs on tumor growth, mTOR pathway, autophagy and apoptosis. CQ alone and in combination with RAD001 significantly decreased neoplasm volume. Histopathological analysis revealed that the combination of CQ and RAD001 markedly inhibited mTOR activity and neoplasm cell growth, along with accumulation of autophagosomes and increased apoptosis. In conclusion, CQ enhances the anti-tumorigenic effect of RAD001 in vivo by inhibiting autophagy. Clinical trials addressing the effects of CQ therapy on neoplasm progression in patients with NENs, mainly in those treated with mTORi, are warranted.

scholarly journals Nme1 and Nme2 genes exert metastasis-suppressor activities in a genetically engineered mouse model of UV-induced melanoma

2020 ◽  
Vol 124 (1) ◽  
pp. 161-165
Author(s):  
Nidhi Pamidimukkala ◽  
Gemma S. Puts ◽  
M. Kathryn Leonard ◽  
Devin Snyder ◽  
Sandrine Dabernat ◽  
...  
Keyword(s):  
Mouse Model ◽  
Suppressor Gene ◽  
Genetically Engineered ◽  
In Vivo Model ◽  
Metastasis Suppressor ◽  
Specific Context ◽  
Genetically Engineered Mouse Model ◽  
Metastatic Activity ◽  
First Time

AbstractNME1 is a metastasis-suppressor gene (MSG), capable of suppressing metastatic activity in cell lines of melanoma, breast carcinoma and other cancer origins without affecting their growth in culture or as primary tumours. Herein, we selectively ablated the tandemly arranged Nme1 and Nme2 genes to assess their individual impacts on metastatic activity in a mouse model (HGF:p16−/−) of ultraviolet radiation (UVR)-induced melanoma. Metastatic activity was strongly enhanced in both genders of Nme1- and Nme2-null mice, with stronger activity in females across all genotypes. The study ascribes MSG activity to Nme2 for the first time in an in vivo model of spontaneous cancer, as well as a novel metastasis-suppressor function to Nme1 in the specific context of UVR-induced melanoma.

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.

scholarly journals X-ray Scatter Imaging of Hepatocellular Carcinoma in a Mouse Model Using Nanoparticle Contrast Agents

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Danielle Rand ◽  
Zoltan Derdak ◽  
Rolf Carlson ◽  
Jack R. Wands ◽  
Christoph Rose-Petruck
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mouse Model ◽  
Contrast Agents ◽  
Malignant Tumors ◽  
Detection Methods ◽  
X Rays ◽  
X Ray ◽  
Enhanced Sensitivity ◽  
X Ray Imaging

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

Establishment of Bioluminescence Imaging Based Leukemia In Vivo Model for Preclinical Testing

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4879-4879
Author(s):  
Myoung Woo Lee ◽  
Hye Jin Kim ◽  
Dae Seong Kim ◽  
Meong Hi Son ◽  
Soo Hyun Lee ◽  
...  
Keyword(s):  
Animal Model ◽  
Mouse Model ◽  
Drug Screening ◽  
Scid Mouse ◽  
Lymphoblastic Leukemia ◽  
Cancer Drug ◽  
Screening System ◽  
Bioluminescent Signal ◽  
Anti Cancer

Abstract Abstract 4879 Background. A hematological malignant animal model is an essential tool for evaluating efficacy of anti-cancer drugs and elucidating underlying mechanism of leukemogenesis. Intraperitoneal (IP) and intravenous (IV) xenograft of acute lymphoblastic leukemia (ALL) cells have limited capacity as in vivo anti-cancer drug screening system. Purpose. In this study, we aimed to establish an ALL animal model using NOD/SCID mouse and evaluate efficiency and sensitivity of the model as a preclinical drug screening system. Materials and Methods. Firefly luciferase (fLuc)-gene introduced ALL (ALL/fLuc) cell line and patient-originated ALL cells were transplanted into a tibia of NOD/SCID mouse. We conducted a comparative analysis of intra-bone marrow (IBMT) transplanted leukemia model with IP and IV transplantation of leukemic cells. Results. IBMT of ALL/fLuc cells effectively established a bioluminescent leukemia NOD/SCID mouse model. Upon comparison of IBMT model with IP and IV transplantation models, infusing identical number of ALL/fLuc cells into NOD/SCID mice resulted in IBMT model with evaluable bioluminescent signal, but not in IP and IV models. In IBMT model, bioluminescent signals of ALL/fLuc cells emitted from peripheral blood, tibia and infiltrated organs indicated that leukemia model was established. The changes in these signals' strength reflected dose-dependent cytotoxic effects of vincristine, which allowed leukemia model with evaluable bioluminescent signal to be utilized as a preclinical drug screening system. IBMT leukemia model was also established using primary ALL cells that can provide additional insights for the development of leukemia therapeutics. Conclusion. IBMT of ALL/fLuc cells enables development of leukemia mouse model with the greater bioluminescent sensitivity than IP and IV in NOD/SCID to evaluate candidate for development of anti-cancer drug. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunoglobulin Attenuates Streptokinase-Mediated Virulence inStreptococcus dysgalactiae Subspeciesequisimilis Necrotizing Fasciitis

2017 ◽  
Vol 217 (2) ◽  
pp. 270-279 ◽  
Author(s):  
Federica Andreoni ◽  
Fabio Ugolini ◽  
Nadia Keller ◽  
Andrina Neff ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Mouse Model ◽  
Necrotizing Fasciitis ◽  
Protective Role ◽  
Specific Antibodies ◽  
Blocking Antibodies ◽  
First Time ◽  
Very High

Abstract Background Necrotizing fasciitis (NF) retains a very high mortality rate despite prompt and adequate antibiotic treatment and surgical debridement. Necrotizing fasciitis has recently been associated withStreptococcus dysgalactiae subspeciesequisimilis (SDSE). Methods We investigated the causes of a very severe clinical manifestation of SDSE-NF by assessing both host and pathogen factors. Results We found a lack of streptokinase-function blocking antibodies in the patient resulting in increased streptokinase-mediated fibrinolysis and bacterial spread. At the same time, the clinical SDSE isolate produced very high levels of streptokinase. Exogenous immunoglobulin Gs (ex-IgGs) efficiently blocked streptokinase-mediated fibrinolysis in vitro, indicating a protective role against the action of streptokinase. In vivo, SDSE infection severity was also attenuated by ex-IgGs in a NF mouse model. Conclusions These findings illustrate for the first time that the lack of specific antibodies against streptococcal virulence factors, such as streptokinase, may contribute to NF disease severity. This can be counteracted by ex-IgGs.

scholarly journals LpCat1 Promotes Malignant Transformation of Hepatocellular Carcinoma Cells by Directly Suppressing STAT1

2021 ◽  
Vol 11 ◽  
Author(s):  
Weidan Ji ◽  
Zhangxiao Peng ◽  
Bin Sun ◽  
Lei Chen ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Clinical Gene Therapy ◽  
First Time ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is a malignant cancer with rapid proliferation and high metastasis ability. To explore the crucial genes that maintain the aggressive behaviors of cancer cells is very important for clinical gene therapy of HCC. LpCat1 was reported to be highly expressed and exert pro-tumorigenic effect in a variety of cancers, including HCC. However, its detailed molecular mechanism remained unclear. In this study, we confirmed that LpCat1 was up-regulated in HCC tissues and cancer cell lines. The overexpressed LpCat1 promoted the proliferation, migration and invasion of HCC cells, and accelerated cell cycle progression, while knocking down LpCat1 significantly inhibited cell proliferation, migration and invasion in vitro and in vivo, and arrested HCC cells at G0/G1 phase. Moreover, we proved for the first time that LpCat1 directly interacted with STAT1 which was generally recognized as a tumor suppressor in HCC. High levels of LpCat1 in HCC could inhibit STAT1 expression, up-regulate CyclinD1, CyclinE, CDK4 and MMP-9, and decrease p27kip1 to promote cancer progression. Conversely, down-regulation of LpCat1 would cause the opposite changes to repress the viability and motility of HCC cells. Consequently, we concluded that LpCat1 was a contributor to progression and metastasis of HCC by interacting with STAT1.

Effect of AdipoR agonist in cholangiocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 323-323
Author(s):  
Khac Cuong Bui ◽  
Mai Ly Thi Nguyen ◽  
Samarpita Barat ◽  
Xi Chen ◽  
Vikas Bhuria ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mouse Model ◽  
Cell Lines ◽  
Colony Formation ◽  
Tumor Burden ◽  
Potential Candidate ◽  
Anti Cancer ◽  
Apoptosis Assay

323 Background: Adiponectin is the key adipokine, which plays an important role in health and disease such as obesity, diabetes, and cancer. Adiponectin is reduced in different tumor types, especially in obesity-related cancer, and recent studies showed that Adiponectin had a potential anti-cancer effect. Obesity is a risk factor for various tumor diseases including cholangiocarcinoma (CC), the second most common primary hepatic cancer. The aim of this study is to investigate for the first time the anti-cancer effect of AdipoR agonist in CC cell lines and a CC engineered mouse model. Methods: Human CC cell lines (TFK-1 and SZ-1) and CC engineered mice (Alb-Cre/KRASG12D/p53L/L) were used to investigate the anti-cancer effects of an AdipoR agonist (2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide). Cell proliferation, migration, invasion, colony formation, apoptosis assay were applied to evaluate the effect of AdipoR agonist in vitro. In addition, important cancer signalling pathways and targets were analysed by Western Blot. Mice (n = 12) were treated with AdipoR or verhicle and tumor burden and survival were monitored. Results: AdipoR agonist suppressed proliferation, migration, invasion, colony formation and apoptosis in CC cells. AdipoR agonist regulated the expression of different proteins such as EMT markers, pAMPK, pSTAT3, and PARP, which have pivotal functions in cholangiocarcinogenesis. AdipoR agonist also prolonged survival time in a CC engineered mouse model. Conclusions: Our data revealed that AdipoR agonist inhibited successfully cell proliferation, migration, invasion, colony formation and apoptosis in vitro, and prolonged mice survival in vivo through regulation of crucial signaling pathways in cholangiocarcinogenesis. These results suggested that AdipoR agonist might become a new potential candidate for CC treatment in the future.

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