scholarly journals Characteristics of in Vivo Model Systems for Ovarian Cancer Studies

Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 120 ◽  
Author(s):  
Tudrej ◽  
Kujawa ◽  
Cortez ◽  
Lisowska
Keyword(s):  
Ovarian Cancer ◽  
Animal Models ◽  
Xenograft Model ◽  
Cellular Migration ◽  
Model Systems ◽  
In Vivo Model ◽  
Preclinical Studies ◽  
Cell Of Origin ◽  
Mice Model ◽  
Mesenchymal Transition

An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response.

Combining galiximab with the chemotherapeutic agents fludarabine or doxorubicin improves efficacy in animal models of lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3040-3040 ◽  
Author(s):  
H. K. Hariharan ◽  
T. Murphy ◽  
D. Clanton ◽  
L. Berquist ◽  
P. Chu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Clinical Benefit ◽  
Therapeutic Potential ◽  
Xenograft Model ◽  
Chemotherapeutic Agents ◽  
Model Systems ◽  
Anti Cd20

3040 Background: Galiximab, a primatized monoclonal antibody that binds with high affinity to CD80 and mediates antibody- dependent, cell-mediated cytotoxicity in vitro, is currently under investigation for the treatment of follicular non-Hodgkin’s lymphoma (NHL). In a phase I/II monotherapy study, galiximab produced an overall response rate of 11%, and tumor reductions were observed in 46% of patients. Initial clinical trials also demonstrate that galiximab is well tolerated and suggest that combining galiximab with rituximab (anti-CD20) provides clinical benefit. These results are consistent with preclinical studies in murine lymphoma xenograft model systems, which demonstrate the superiority of combination therapy. Methods: To further define the therapeutic potential of galiximab, the Raji subcutaneous and the SKW disseminated lymphoma murine xenograft models were used to define the in vivo efficacy of galiximab alone or in combination with fludarabine or doxorubicin. Similar studies were performed with rituximab. Results: In the Raji model, both galiximab and rituximab exhibited maximal inhibition of the growth of preestablished (150-mg) tumors at a dose of 3 mg/kg/wk. Interestingly, higher doses of galiximab (but not rituximab) showed reduced inhibition. Galiximab (3 mg/kg/wk) inhibited tumor growth alone (P<0.0001 vs. control) and showed significantly enhanced activity when combined with fludarabine (50 or 100 mg/kg daily for 5 days; P<0.0002 vs. galiximab alone and P<0.003 vs. fludarabine alone). Similar results were observed with rituximab. In the SKW model, treatment with galiximab (5 mg/kg/wk for 6 doses) significantly enhanced survival compared with a control (P<0.0001) or doxorubicin (2.5 mg/kg/day for 3 doses; P<0.0001). Studies combining fludarabine or doxorubicin with both galiximab and rituximab are ongoing. Conclusions: Studies in animal models of lymphoma indicate that galiximab may provide clinical benefit when used in combination with chemotherapeutic agents such as fludarabine and doxorubicin, and provide a rationale for the investigation of these novel chemoimmunotherapy combinations in clinical trials. No significant financial relationships to disclose.

scholarly journals Improving gastric cancer preclinical studies using diverse in vitro and in vivo model systems

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Hae Ryung Chang ◽  
Hee Seo Park ◽  
Young Zoo Ahn ◽  
Seungyoon Nam ◽  
Hae Rim Jung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Model Systems ◽  
In Vivo Model ◽  
Preclinical Studies

scholarly journals Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition

2019 ◽  
Vol 116 (51) ◽  
pp. 25880-25890 ◽  
Author(s):  
Ileana C. Cuevas ◽  
Subhransu S. Sahoo ◽  
Ashwani Kumar ◽  
He Zhang ◽  
Jill Westcott ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Genetic Model ◽  
Precancerous Lesions ◽  
Lineage Tracing ◽  
Model Systems ◽  
Cancer Type ◽  
Cell Of Origin ◽  
Uterine Carcinosarcoma ◽  
Mesenchymal Transition

Uterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such asTp53andPten. However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressorFbxw7in endometrial cancer through defined genetic model systems. Inactivation ofFbxw7andPtenresulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquiredTrp53mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial–mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.

scholarly journals New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact

2008 ◽  
Vol 26 (32) ◽  
pp. 5284-5293 ◽  
Author(s):  
Keren Levanon ◽  
Christopher Crum ◽  
Ronny Drapkin
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Genetic Alterations ◽  
Model Systems ◽  
Evolutionary Stage ◽  
High Grade ◽  
Cell Of Origin ◽  
Neoplastic Tissue ◽  
Cancer Pathogenesis ◽  
Binary Model

There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.

scholarly journals Tumor-Derived Extracellular Vesicles Promote Activation of Carcinoma-Associated Fibroblasts and Facilitate Invasion and Metastasis of Ovarian Cancer by Carrying miR-630

2021 ◽  
Vol 9 ◽  
Author(s):  
Yulan Cui ◽  
Deying Wang ◽  
Min Xie
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Carcinoma Associated Fibroblasts

Ovarian cancer (OC) is a lethal gynecological malignancy. Extracellular vesicles (EVs) are crucial media in cell-to-cell communication by carrying microRNAs (miRs). The current study aims to investigate the underlying mechanism of miR-630 carried by OC cell-derived EVs in regard to invasion and metastasis of OC cells. miRs related to OC metastasis were searched and screened. The expression patterns of screened miRs in human normal fibroblasts (NFs) and carcinoma-associated fibroblasts (CAFs) were detected using RT-qPCR. miR-630 related to OC metastasis and CAFs activation was analyzed further. The levels of FAP and α-SMA were detected using Western blotting and immunofluorescence. The migration of NFs was measured using Transwell assay. OC cell-derived EVs were isolated and identified. Uptake of EVs by NFs was observed using immunofluorescence staining. The culture supernatant of NFs was collected and used to culture the low metastasis cell line OVCAR8. The migration and invasion of OC cells and epithelial mesenchymal transition (EMT) were measured. Moreover, a xenograft model was established by injecting OVCAR8 cells of different groups into nude mice. Lastly, the effect of EV-pretreated NFs on invasion and metastasis of OC cells was observed in vivo. miR-630 was upregulated in OC cells and CAFs, and further associated with CAF activation and OC metastasis. miR-630 overexpression increased the levels of FAP and α-SMA in NFs, resulting in the transformation of NFs into CAFs. EVs carried miR-630 into NFs and EVs promoted CAF activation. miR-630 targeted KLF6. miR-630 inhibition or KLF6 overexpression attenuated EVs-induced CAF activation. EVs activated the NF-κB pathway via the miR-630/KLF6 axis. The conditioned medium of NFs pretreated with EVs promoted the invasion and metastasis of OVCAR8 cells, while downregulating miR-630 in EVs partially inhibited the promotive effect of NFs. EV-pretreated NFs promoted invasion and metastasis of OC in vivo. In conclusion, EVs carried miR-630 into NFs, thereby facilitating CAF activation and promoting invasion and metastasis of OC by inhibiting KLF6 and activating the NF-κB pathway. Our findings might offer a novel mechanism of invasion and metastasis of OC from the perspective of tumor microenvironment.

scholarly journals Animal models of MEN1

2017 ◽  
Vol 24 (10) ◽  
pp. T161-T177 ◽  
Author(s):  
Hermine Mohr ◽  
Natalia S Pellegata
Keyword(s):  
Animal Models ◽  
Therapy Response ◽  
Model Systems ◽  
Preclinical Studies ◽  
Hormonal Changes ◽  
Novel Therapies ◽  
Loss Of Function ◽  
Potential Models ◽  
Novel Drugs ◽  
Future Patient

Animal models of cancer have been instrumental in advancing our understanding of the biology of tumor initiation and progression, in studying gene function and in performing preclinical studies aimed at testing novel therapies. Several animal models of the MEN1 syndrome have been generated in different organisms by introducing loss-of-function mutations in the orthologues of the humanMEN1gene. In this review, we will discuss MEN1 and MEN1-like models in Drosophila, mice and rats. These model systems with their specific advantages and limitations have contributed to elucidate the function of Menin in tumorigenesis, which turned out to be remarkably conserved from flies to mammals, as well as the biology of the disease. Mouse models of MEN1 closely resemble the human disease in terms of tumor spectrum and associated hormonal changes, although individual tumor frequencies are variable. Rats affected by the MENX (MEN1-like) syndrome share some features with MEN1 patients albeit they bear a germline mutation inCdkn1b(p27) and not inMen1. BothMen1-knockout mice and MENX rats have been exploited for therapy-response studies testing novel drugs for efficacy against neuroendocrine tumors (NETs) and have provided promising leads for novel therapies. In addition to presenting well-established models of MEN1, we also discuss potential models which, if implemented, might broaden even further our knowledge of neuroendocrine tumorigenesis. In the future, patient-derived xenografts in zebrafish or mice might allow us to expand the tool-box currently available for preclinical studies of MEN1-associated tumors.

scholarly journals The Microbiota and Gut-Related Disorders: Insights from Animal Models

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2401 ◽  
Author(s):  
Layla Kamareddine ◽  
Hoda Najjar ◽  
Muhammad Umar Sohail ◽  
Hadil Abdulkader ◽  
Maha Al-Asmakh
Keyword(s):  
Animal Models ◽  
Gut Microbiota ◽  
Defense Mechanisms ◽  
Metabolic Diseases ◽  
Fruit Fly ◽  
Model Systems ◽  
Model Organisms ◽  
Host Immune System ◽  
Mice Model ◽  
Host Microbe Interactions

Over the past decade, the scientific committee has called for broadening our horizons in understanding host–microbe interactions and infectious disease progression. Owing to the fact that the human gut harbors trillions of microbes that exhibit various roles including the production of vitamins, absorption of nutrients, pathogen displacement, and development of the host immune system, particular attention has been given to the use of germ-free (GF) animal models in unraveling the effect of the gut microbiota on the physiology and pathophysiology of the host. In this review, we discuss common methods used to generate GF fruit fly, zebrafish, and mice model systems and highlight the use of these GF model organisms in addressing the role of gut-microbiota in gut-related disorders (metabolic diseases, inflammatory bowel disease, and cancer), and in activating host defense mechanisms and amending pathogenic virulence.

Sign in / Sign up

Export Citation Format

Share Document