scholarly journals Animal models of colorectal peritoneal metastasis

2016 ◽  
Vol 1 (1) ◽  
pp. 23-43 ◽  
Author(s):  
Félix Gremonprez ◽  
Wouter Willaert ◽  
Wim Ceelen
Keyword(s):  
Colorectal Cancer ◽  
Animal Models ◽  
Peritoneal Carcinomatosis ◽  
Peritoneal Metastasis ◽  
Treatment Options ◽  
Genetically Engineered ◽  
Preclinical Research ◽  
Novel Treatment ◽  
Genetically Engineered Mice ◽  
Wide Range

AbstractColorectal cancer remains an important cause of mortality worldwide. The presence of peritoneal carcinomatosis (PC) causes significant symptoms and is notoriously difficult to treat. Therefore, informative preclinical research into the mechanisms and possible novel treatment options of colorectal PC is essential in order to improve the prognostic outlook in these patients. Several syngeneic and xenograft animal models of colorectal PC were established, studying a wide range of experimental procedures and substances. Regrettably, more sophisticated models such as those giving rise to spontaneous PC or involving genetically engineered mice are lacking. Here, we provide an overview of all reported colorectal PC animal models and briefly discuss their use, strengths, and limitations.

scholarly journals Animal Models of Colorectal Cancer: From Spontaneous to Genetically Engineered Models and Their Applications

2021 ◽  
Vol 8 (4) ◽  
pp. 59
Author(s):  
Elisabete Nascimento-Gonçalves ◽  
Bruno A.L. Mendes ◽  
Rita Silva-Reis ◽  
Ana I. Faustino-Rocha ◽  
Adelina Gama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Animal Models ◽  
Cancer Progression ◽  
Social Impact ◽  
Genetically Engineered ◽  
In Vivo Studies ◽  
Gastrointestinal Malignancies ◽  
Advantages And Disadvantages ◽  
Colon Cancer Progression

Colorectal cancer is one of the most common gastrointestinal malignancies in humans, affecting approximately 1.8 million people worldwide. This disease has a major social impact and high treatment costs. Animal models allow us to understand and follow the colon cancer progression; thus, in vivo studies are essential to improve and discover new ways of prevention and treatment. Dietary natural products have been under investigation for better and natural prevention, envisioning to show their potential. This manuscript intends to provide the readers a review of rodent colorectal cancer models available in the literature, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds’ effects on colorectal cancer.

Is the hypotensive effect of clonidine and related drugs due to imidazoline binding sites?

1997 ◽  
Vol 273 (5) ◽  
pp. R1580-R1584 ◽  
Author(s):  
Patrice G. Guyenet
Keyword(s):  
Binding Sites ◽  
Hypotensive Effect ◽  
Genetically Engineered ◽  
Therapeutic Effects ◽  
Genetically Engineered Mice ◽  
Wide Range ◽  
The Central Nervous System ◽  
Imidazoline Binding Sites ◽  
Cellular Components

Clonidine and related α2-adrenergic receptor (α2AR) agonists lower arterial pressure primarily by an action within the central nervous system. These drugs also have varying degrees of affinity for other cellular components called nonadrenergic imidazoline binding sites (NAIBS). For over 20 years, the α2AR agonist activity of clonidine-like drugs was thought to account for their therapeutic effects (α2 theory). However, several groups have recently proposed a competing “imidazoline theory” according to which the hypotensive effect of clonidine-like drugs would in fact owe more to their affinity for one type of NAIBS, called I1receptors. The α2-theory is strongly supported by four main types of congruent data. First, the hypotensive effect of systemically administered clonidine is blocked by α2AR antagonists that are without affinity for I1 NAIBs. Second, the hypotensive effect of intravenous clonidine is absent in genetically engineered mice in which a defective α2AAR has been substituted for the normal one. Third, the sympatholytic effect of clonidine is consistent with the presence of conventional inhibitory α2ARs on sympathetic preganglionic neurons and on their main excitatory inputs in the medulla oblongata. Fourth, the first I1 ligand without affinity for α2ARs was found to be biologically inactive. The imidazoline theory is supported by a limited repertoire of whole animal “in vivo” pharmacological experiments that remain open to a wide range of interpretations. In conclusion, the bulk of the evidence strongly supports a largely predominant role of α2AR mechanisms in the action of most clonidine-like agents at therapeutically relevant doses or concentrations. Even the small pharmacological differences between these agents cannot yet be linked with certainty to their relative affinity for I1 NAIBS.

scholarly journals Emerging and Evolving Ovarian Cancer Animal Models

2015 ◽  
Vol 8s1 ◽  
pp. CGM.S21221 ◽  
Author(s):  
Alexander S. Bobbs ◽  
Jennifer M. Cole ◽  
Karen D. Cowden Dahl
Keyword(s):  
Ovarian Cancer ◽  
Animal Models ◽  
Mouse Models ◽  
Immune Cell ◽  
Treatment Options ◽  
The United States ◽  
Genetically Engineered ◽  
Response To Therapy ◽  
Gynecological Malignancy ◽  
Immunocompetent Mice

Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect metastasis, response to therapy, and diverse genetics found in patients. Additionally, multiple genetically engineered mouse models have increased our understanding of possible tissues of origin for OC and what role individual mutations play in establishing ovarian tumors. Many of these models are used to test novel therapeutics. As no single model perfectly copies the human disease, we can use a variety of OC animal models in hypothesis testing that will lead to novel treatment options. The goal of this review is to provide an overview of the utility of different mouse models in the study of OC and their suitability for cancer research.

Caveolin-1, tetraspanin CD81 and flotillins in lymphocyte cell membrane organization, signaling and immunopathology

2020 ◽  
Vol 48 (6) ◽  
pp. 2387-2397
Author(s):  
Anna-Maria Schaffer ◽  
Susana Minguet
Keyword(s):  
Immune System ◽  
Intracellular Signaling ◽  
Antigen Receptor ◽  
Lymphocyte Activation ◽  
Genetically Engineered ◽  
Future Research ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Genetically Engineered Mice ◽  
Wide Range

The adaptive immune system relies on B and T lymphocytes to ensure a specific and long-lasting protection of an individual from a wide range of potential pathogenic hits. Lymphocytes are highly potent and efficient in eliminating pathogens. However, lymphocyte activation must be tightly regulated to prevent incorrect activity that could result in immunopathologies, such as autoimmune disorders or cancers. Comprehensive insight into the molecular events underlying lymphocyte activation is of enormous importance to better understand the function of the immune system. It provides the basis to design therapeutics to regulate lymphocyte activation in pathological scenarios. Most reported defects in immunopathologies affect the regulation of intracellular signaling pathways. This highlights the importance of these molecules, which control lymphocyte activation and homeostasis impacting lymphocyte tolerance to self, cytokine production and responses to infections. Most evidence for these defects comes from studies of disease models in genetically engineered mice. There is an increasing number of studies focusing on lymphocytes derived from patients which supports these findings. Many indirectly involved proteins are emerging as unexpected regulators of the immune system. In this mini-review, we focus in proteins that regulate plasma membrane (PM) compartmentalization and thereby impact the steady state and the activation of immunoreceptors, namely the T cell antigen receptor (TCR) and the B cell antigen receptor (BCR). Some of these membrane proteins are shown to be involved in immune abnormalities; others, however, are not thoroughly investigated in the context of immune pathogenesis. We aim to highlight them and stimulate future research avenues.

scholarly journals A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yasuhiro Kazuki ◽  
Feng J Gao ◽  
Yicong Li ◽  
Anna J Moyer ◽  
Benjamin Devenney ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Human Chromosome ◽  
Treatment Options ◽  
Artificial Chromosome ◽  
Chromosome 21 ◽  
Preclinical Research ◽  
Human Chromosome 21 ◽  
Genetic Mouse Model ◽  
Wide Range

Animal models of Down syndrome (DS), trisomic for human chromosome 21 (HSA21) genes or orthologs, provide insights into better understanding and treatment options. The only existing transchromosomic (Tc) mouse DS model, Tc1, carries a HSA21 with over 50 protein coding genes (PCGs) disrupted. Tc1 is mosaic, compromising interpretation of results. Here, we “clone” the 34 MB long arm of HSA21 (HSA21q) as a mouse artificial chromosome (MAC). Through multiple steps of microcell-mediated chromosome transfer, we created a new Tc DS mouse model, Tc(HSA21q;MAC)1Yakaz (“TcMAC21”). TcMAC21 is not mosaic and contains 93% of HSA21q PCGs that are expressed and regulatable. TcMAC21 recapitulates many DS phenotypes including anomalies in heart, craniofacial skeleton and brain, molecular/cellular pathologies, and impairments in learning, memory and synaptic plasticity. TcMAC21 is the most complete genetic mouse model of DS extant and has potential for supporting a wide range of basic and preclinical research.

scholarly journals Steryl Glycosides in Fungal Pathogenesis: An Understudied Immunomodulatory Adjuvant

2020 ◽  
Vol 6 (1) ◽  
pp. 25 ◽  
Author(s):  
Tyler G. Normile ◽  
Kyle McEvoy ◽  
Maurizio Del Poeta
Keyword(s):  
Immune Response ◽  
Fungal Infections ◽  
Treatment Options ◽  
Host Immune Response ◽  
Novel Treatment ◽  
Wide Range ◽  
Efficacious Vaccine ◽  
Lipid Compounds ◽  
Fungal Interactions

Invasive fungal infections pose an increasing threat to human hosts, especially in immunocompromised individuals. In response to the increasing morbidity and mortality of fungal infections, numerous groups have shown great strides in uncovering novel treatment options and potential efficacious vaccine candidates for this increasing threat due to the increase in current antifungal resistance. Steryl glycosides are lipid compounds produced by a wide range of organisms, and are largely understudied in the field of pathogenicity, especially to fungal infections. Published works over the years have shown these compounds positively modulating the host immune response. Recent advances, most notably from our lab, have strongly indicated that steryl glycosides have high efficacy in protecting the host against lethal Cryptococcal infection through acting as an immunoadjuvant. This review will summarize the keystone studies on the role of steryl glycosides in the host immune response, as well as elucidate the remaining unknown characteristics and future perspectives of these compounds for the host–fungal interactions.

Metabolic Syndrome is a Risk Factor for Post-Operative Adhesions: Need for Novel Treatment Strategies

2018 ◽  
Vol 51 (01) ◽  
pp. 35-41 ◽  
Author(s):  
Yair Pilpel ◽  
Guy Pines ◽  
Andreas Birkenfeld ◽  
Stefan Bornstein ◽  
Rafael Miller
Keyword(s):  
Metabolic Syndrome ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Postoperative Adhesions ◽  
Invasive Procedures ◽  
Novel Treatment ◽  
Number Of Patients ◽  
Wide Range ◽  
Novel Treatment Strategies

AbstractMetabolic syndrome is a group of disorders which include obesity, diabetes, dyslipidemias, and hypertension. This condition is rapidly increasing in an aging population. The rates of surgery in older patients is also growing and a wide range of operations including minimally invasive procedures is now available for this segment of the population. The number of patients suffering from postoperative adhesions is therefore correspondingly increasing. In addition to preventing and treating the metabolic disease itself, improved therapeutic strategies for the prevention of surgical adhesions have to be developed. Here we review the existing and novel treatment options.

scholarly journals Manipulation of DNA Repair Proficiency in Mouse Models of Colorectal Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Michael A. Mcilhatton ◽  
Gregory P. Boivin ◽  
Joanna Groden
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Mouse Models ◽  
Cancer Biology ◽  
Genetically Engineered ◽  
Biologically Relevant ◽  
Dna Repair Mechanisms ◽  
Genetically Engineered Mice ◽  
Repair Mechanisms

Technical and biological innovations have enabled the development of more sophisticated and focused murine models that increasingly recapitulate the complex pathologies of human diseases, in particular cancer. Mouse models provide excellentin vivosystems for deciphering the intricacies of cancer biology within the context of precise experimental settings. They present biologically relevant, adaptable platforms that are amenable to continual improvement and refinement. We discuss how recent advances in our understanding of tumorigenesis and the underlying deficiencies of DNA repair mechanisms that drive it have been informed by using genetically engineered mice to create defined, well-characterized models of human colorectal cancer. In particular, we focus on how mechanisms of DNA repair can be manipulated precisely to createin vivomodels whereby the underlying processes of tumorigenesis are accelerated or attenuated, dependent on the composite alleles carried by the mouse model. Such models have evolved to the stage where they now reflect the initiation and progression of sporadic cancers. The review is focused on mouse models of colorectal cancer and how insights from these models have been instrumental in shaping our understanding of the processes and potential therapies for this disease.

scholarly journals Ovarian Cancer Animal Models for Preclinical Studies and Development of Ovarian Cancer Drugs

2019 ◽  
Vol 17 (2) ◽  
pp. 139
Author(s):  
Ni Made Dwi Sandhiutami ◽  
Puspita Eka Wuyung ◽  
Wawaimuli Arozal ◽  
Melva Louisa ◽  
Deni Rahmat
Keyword(s):  
Ovarian Cancer ◽  
Animal Models ◽  
Treatment Strategies ◽  
Reproductive Factors ◽  
Experimental Models ◽  
Genetically Engineered ◽  
Human Ovarian Cancer ◽  
Preneoplastic Lesions ◽  
Genetically Engineered Mice ◽  
New Treatment

Treatment for ovarian carcinoma is still far from optimal, animal models are still needed to study human epithelial ovarian cancer. Animal models of ovarian cancer are very important for understanding the pathogenesis of the disease and for testing new treatment strategies. Ovarian carcinogenesis models in mice have been modified and repaired to produce preneoplastic lesions and neoplastic ovaries that are pathogens resembling human ovarian cancer. Although spontaneous ovarian tumors in mice have been reported, some of the shortcomings of existing studies preclude their use as animal models of ovarian cancer. Because of this, many efforts have been made to develop animal models that are relevant for ovarian cancer. Experimental animal models are developed accurately to represent cellular and molecular changes associated with the initiation and development of human ovarian cancer. Accurate experimental models have significant potential in facilitating the development of better methods for early detection and treatment of ovarian cancer. Several animal models of ovarian cancer have been reported, including manipulation of various reproductive factors or exposure to carcinogens. The latest advance in ovarian cancer modeling is using genetically engineered mice.

scholarly journals Animal Models of Adenomyosis

2020 ◽  
Vol 38 (02/03) ◽  
pp. 168-178
Author(s):  
Ryan M. Marquardt ◽  
Jae-Wook Jeong ◽  
Asgerally T. Fazleabas
Keyword(s):  
Animal Models ◽  
Nonhuman Primates ◽  
Case Reports ◽  
Treatment Options ◽  
Genetically Engineered ◽  
Therapeutic Interventions ◽  
Future Directions ◽  
Efficacious Treatment ◽  
Insight Into ◽  
Preclinical Screening

AbstractAdenomyosis is a nonmalignant uterine disorder in which endometrial tissue exists within and grows into the myometrium. Animal models have generated limited insight into the still-unclear pathogenesis of adenomyosis, provided a platform for preclinical screening of many drugs and compounds with potential as therapeutics, and elucidated mechanisms underlying the pain and fertility issues that occur in many women with the disease. Spontaneous adenomyosis has been studied in nonhuman primates, primarily in the form of case reports. Adenomyosis is routinely experimentally induced in mice through methods such as neonatal tamoxifen exposure, pituitary engraftment, and human tissue xenotransplantation. Several studies have also reported hormonal or environmental toxicant exposures that give rise to murine adenomyosis, and genetically engineered models have been created that recapitulate the human-like condition, most notably involving alteration of β-catenin expression. This review describes the animal models for adenomyosis and their contributions to our understanding of the factors underpinning the development of symptoms. Animal models represent a unique opportunity for understanding the molecular basis of adenomyosis and developing efficacious treatment options for affected women. Herein, we assess their different potentials and limitations with regard to identification of new therapeutic interventions and reflect on future directions for research and drug validation.

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