scholarly journals Xenograft Zebrafish Models for the Development of Novel Anti-Hepatocellular Carcinoma Molecules

2021 ◽  
Vol 14 (8) ◽  
pp. 803
Author(s):  
Federica Tonon ◽  
Rossella Farra ◽  
Cristina Zennaro ◽  
Gabriele Pozzato ◽  
Nhung Truong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Husbandry ◽  
Therapeutic Strategies ◽  
Common Type ◽  
Transgenic Zebrafish ◽  
Therapeutic Approaches ◽  
Predisposing Factor ◽  
Different Types ◽  
Xenograft Models ◽  
Tumor Related Death

Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New therapeutic strategies are therefore urgently needed. The use of animal models represents a relevant tool for preclinical screening of new molecules/strategies against HCC. However, several issues, including animal husbandry, limit the use of current models (rodent/pig). One animal model that has attracted the attention of the scientific community in the last 15 years is the zebrafish. This freshwater fish has several attractive features, such as short reproductive time, limited space and cost requirements for husbandry, body transparency and the fact that embryos do not show immune response to transplanted cells. To date, two different types of zebrafish models for HCC have been developed: the transgenic zebrafish and the zebrafish xenograft models. Since transgenic zebrafish models for HCC have been described elsewhere, in this review, we focus on the description of zebrafish xenograft models that have been used in the last five years to test new molecules/strategies against HCC.

scholarly journals Adeno-Associated Viral Vectors as Versatile Tools for Parkinson’s Research, Both for Disease Modeling Purposes and for Therapeutic Uses

2021 ◽  
Vol 22 (12) ◽  
pp. 6389
Author(s):  
Ana Fajardo-Serrano ◽  
Alberto J. Rico ◽  
Elvira Roda ◽  
Adriana Honrubia ◽  
Sandra Arrieta ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Viral Vectors ◽  
Disease Modeling ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Therapeutic Uses ◽  
Different Types ◽  
Experimental Challenge

It is without any doubt that precision medicine therapeutic strategies targeting neurodegenerative disorders are currently witnessing the spectacular rise of newly designed approaches based on the use of viral vectors as Trojan horses for the controlled release of a given genetic payload. Among the different types of viral vectors, adeno-associated viruses (AAVs) rank as the ones most commonly used for the purposes of either disease modeling or for therapeutic strategies. Here, we reviewed the current literature dealing with the use of AAVs within the field of Parkinson’s disease with the aim to provide neuroscientists with the advice and background required when facing a choice on which AAV might be best suited for addressing a given experimental challenge. Accordingly, here we will be summarizing some insights on different AAV serotypes, and which would be the most appropriate AAV delivery route. Next, the use of AAVs for modeling synucleinopathies is highlighted, providing potential readers with a landscape view of ongoing pre-clinical and clinical initiatives pushing forward AAV-based therapeutic approaches for Parkinson’s disease and related synucleinopathies.

scholarly journals Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes

2018 ◽  
Vol 11 (3) ◽  
pp. 84 ◽  
Author(s):  
Ana Gomes ◽  
Ana Moreira ◽  
Gonçalo Mesquita ◽  
Maria Gomes
Keyword(s):  
Iron Metabolism ◽  
Recent Literature ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Different Types ◽  
Essential Nutrient ◽  
Living Organisms ◽  
Almost All ◽  
And Control ◽  
Ongoing Infection

Iron is an essential nutrient for almost all living organisms, but is not easily made available. Hosts and pathogens engage in a fight for the metal during an infection, leading to major alterations in the host’s iron metabolism. Important pathological consequences can emerge from the mentioned interaction, including anemia. Several recent reports have highlighted the alterations in iron metabolism caused by different types of infection, and several possible therapeutic strategies emerge, based on the targeting of the host’s iron metabolism. Here, we review the most recent literature on iron metabolism alterations that are induced by infection, the consequent development of anemia, and the potential therapeutic approaches to modulate iron metabolism in order to correct iron-related pathologies and control the ongoing infection.

scholarly journals Recent Advances in Nanotechnology for the Treatment of Melanoma

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 785
Author(s):  
Roberta Cassano ◽  
Massimo Cuconato ◽  
Gabriella Calviello ◽  
Simona Serini ◽  
Sonia Trombino
Keyword(s):  
Carbon Nanotubes ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Therapeutic Strategies ◽  
Multi Drug Resistance ◽  
Therapeutic Approaches ◽  
Innovative Strategy ◽  
Different Types ◽  
Specific Alternative ◽  
Melanoma Patients

Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed.

The comparison of efficacy in 3 different types of pre-coagulation method for endoscopic liver resection of hepatocellular carcinoma

2010 ◽  
Vol 28 ◽  
pp. 47-51 ◽  
Author(s):  
Takatoshi Ishiko ◽  
Toru Beppu ◽  
Akira Chikamoto ◽  
Toshiro Masuda ◽  
Hirohisa Okabe ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Resection ◽  
Different Types

Evaluation of Small Wastewater Treatment Plants in the County of Århus – Denmark

1993 ◽  
Vol 28 (10) ◽  
pp. 33-41
Author(s):  
Jes la Cour Jansen ◽  
Bodil Mose Pedersen ◽  
Erik Moldt
Keyword(s):  
Wastewater Treatment ◽  
Constructed Wetlands ◽  
Biological Treatment ◽  
Wastewater Treatment Plants ◽  
Chemical Precipitation ◽  
Common Type ◽  
Treatment Efficiency ◽  
Effluent Quality ◽  
Different Types

Influent and effluent data from about 120 small wastewater treatment plants (100 - 2000 PE) have been collected and processed. Seven different types of plants are represented. The effluent quality and the treatment efficiency have been evaluated. The most common type of plant is mechanical/biological treatment plants. Some of them are nitrifying and some are also extended for chemical precipitation of phosphorus. Constructed wetlands and biological sandfilters are also represented among the small wastewater treatment plants.

scholarly journals MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-β, and STAT3 Signaling

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 940
Author(s):  
Chi-Yu Lai ◽  
Kun-Yun Yeh ◽  
Chiu-Ya Lin ◽  
Yang-Wen Hsieh ◽  
Hsin-Hung Lai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Stellate Cell ◽  
Human Cancer ◽  
Tumor Formation ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Lipid Metabolism Disorder ◽  
Full Spectrum ◽  
Stat3 Signaling

MicroRNA-21 (miR-21) is one of the most frequently upregulated miRNAs in liver diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). However, mechanistic pathways that connect NAFLD and HCC remain elusive. We developed a doxycycline (Dox)-inducible transgenic zebrafish model (LmiR21) which exhibited an upregulation of miR-21 in the liver, which in turn induced the full spectrum of NAFLD, including steatosis, inflammation, fibrosis, and HCC, in the LmiR21 fish. Diethylnitrosamine (DEN) treatment led to accelerated liver tumor formation and exacerbated their aggressiveness. Moreover, prolonged miR-21 expression for up to ten months induced nonalcoholic steatohepatitis (NASH)-related HCC (NAHCC). Immunoblotting and immunostaining confirmed the presence of miR-21 regulatory proteins (i.e., PTEN, SMAD7, p-AKT, p-SMAD3, and p-STAT3) in human nonviral HCC tissues and LmiR21 models. Thus, we demonstrated that miR-21 can induce NAHCC via at least three mechanisms: First, the occurrence of hepatic steatosis increases with the decrease of ptenb, pparaa, and activation of the PI3K/AKT pathway; second, miR-21 induces hepatic inflammation (or NASH) through an increase in inflammatory gene expression via STAT3 signaling pathways, and induces liver fibrosis through hepatic stellate cell (HSC) activation and collagen deposition via TGF-β/Smad3/Smad7 signaling pathways; finally, oncogenic activation of Smad3/Stat3 signaling pathways induces HCC. Our LmiR21 models showed similar molecular pathology to the human cancer samples in terms of initiation of lipid metabolism disorder, inflammation, fibrosis and activation of the PI3K/AKT, TGF-β/SMADs and STAT3 (PTS) oncogenic signaling pathways. Our findings indicate that miR-21 plays critical roles in the mechanistic perspectives of NAHCC development via the PTS signaling networks.

scholarly journals MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3026
Author(s):  
Hyuk Moon ◽  
Simon-Weonsang Ro
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Erk Signaling ◽  
Health Concern ◽  
Alternative Mechanism ◽  
Major Health ◽  
Activating Mutations ◽  
Genetic Events

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

scholarly journals Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus

2006 ◽  
Vol 5 (7) ◽  
pp. 1091-1103 ◽  
Author(s):  
William J. Steinbach ◽  
Robert A. Cramer ◽  
B. Zachary Perfect ◽  
Yohannes G. Asfaw ◽  
Theodor C. Sauer ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Clinical Observation ◽  
Immunocompromised Patient ◽  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Growth Morphology ◽  
Different Types ◽  
Hyphal Morphology

ABSTRACT Calcineurin is implicated in a myriad of human diseases as well as homeostasis and virulence in several major human pathogenic microorganisms. The fungus Aspergillus fumigatus is a leading cause of infectious death in the rapidly expanding immunocompromised patient population. Current antifungal treatments for invasive aspergillosis are often ineffective, and novel therapeutic approaches are urgently needed. We demonstrate that a mutant of A. fumigatus lacking the calcineurin A (cnaA) catalytic subunit exhibited defective hyphal morphology related to apical extension and polarized growth, which resulted in drastically decreased filamentation. The ΔcnaA mutant lacked the extensive lattice of invading hyphae seen with the wild-type and complemented strains. Sporulation was also affected in the ΔcnaA mutant, including morphological conidial defects with the absence of surface rodlets and the added presence of disjunctors creating long conidial chains. Infection with the ΔcnaA mutant in several distinct animal models with different types of immunosuppression and inoculum delivery led to a profound attenuation of pathogenicity compared to infection with the wild-type and complemented strains. Lung tissue from animals infected with the ΔcnaA mutant showed a complete absence of hyphae, in contrast to tissue from animals infected with the wild-type and complemented strains. Quantitative fungal burden and pulmonary infarct scoring confirmed these findings. Our results support the clinical observation that substantially decreasing fungal growth can prevent disease establishment and decrease mortality. Our findings reveal that calcineurin appears to play a globally conserved role in the virulence of several pathogenic fungi and yet plays specialized roles in each and can be an excellent target for therapeutic intervention.

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