Humanized NOD-SCID IL2rg –/– mice as a preclinical model for cancer research and its potential use for individualized cancer therapies

2014 ◽  
Vol 344 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Qianjun Zhou ◽  
John Facciponte ◽  
Min Jin ◽  
Qiang Shen ◽  
Qiang Lin
2021 ◽  
Vol 10 ◽  
Author(s):  
Yifan Ma ◽  
Shiyan Dong ◽  
Xuefeng Li ◽  
Betty Y. S. Kim ◽  
Zhaogang Yang ◽  
...  

Extracellular vesicles (EVs) are cell-derived membrane particles that represent an endogenous mechanism for cell-to-cell communication. Since discovering that EVs have multiple advantages over currently available delivery platforms, such as their ability to overcome natural barriers, intrinsic cell targeting properties, and circulation stability, the potential use of EVs as therapeutic nanoplatforms for cancer studies has attracted considerable interest. To fully elucidate EVs’ therapeutic function for treating cancer, all current knowledge about cellular uptake and trafficking of EVs will be initially reviewed. In order to further improve EVs as anticancer therapeutics, engineering strategies for cancer therapy have been widely explored in the last decade, along with other cancer therapies. However, therapeutic applications of EVs as drug delivery systems have been limited because of immunological concerns, lack of methods to scale EV production, and efficient drug loading. We will review and discuss recent progress and remaining challenges in developing EVs as a delivery nanoplatform for cancer therapy.


2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Wun-Jae Kim ◽  
Soongang Park ◽  
Yong-June Kim

Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by conventional clinical and pathologic parameters. Here, the current situation in bladder cancer research with respect to identification of suitable prognostic markers is reviewed. A number of individual molecular markers that might predict bladder cancer recurrence and progression have been identified but many are not sufficiently sensitive or specific for the whole spectrum of bladder cancer diseases seen in routine clinical practice. These limitations have led to interest in other molecular parameters that could enable more accurate prognosis for bladder cancer patients. Of particular interest is the epigenetic silencing of tumor suppressor genes. Since the methylation of these genes can correlate with a poor prognosis, the methylation profile may represent a new biomarker that indicates the risk of transitional cell carcinoma development. In addition, bladder cancer research is likely to be revolutionized by high-throughput molecular technologies, which allow rapid and global gene expression analysis of thousands of tumor samples. Initial studies employing these technologies have considerably expanded our ability to classify bladder cancers with respect to their survivability. Future microarray analyses are likely to reveal particular gene expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as patient's survival and responsiveness to different anti-cancer therapies, with great specificity and sensitivity.


2019 ◽  
Vol 3 (1) ◽  
pp. 345-363 ◽  
Author(s):  
Thomas A. O'Loughlin ◽  
Luke A. Gilbert

Functional genomics holds great promise for the dissection of cancer biology. The elucidation of genetic cooperation and molecular details that govern oncogenesis, metastasis, and response to therapy is made possible by robust technologies for perturbing gene function coupled to quantitative analysis of cancer phenotypes resulting from genetic or epigenetic perturbations. Multiplexed genetic perturbations enable the dissection of cooperative genetic lesions as well as the identification of synthetic lethal gene pairs that hold particular promise for constructing innovative cancer therapies. Lastly, functional genomics strategies enable the highly multiplexed in vivo analysis of genes that govern tumorigenesis as well as of the complex multicellular biology of a tumor, such as immune response and metastasis phenotypes. In this review, we discuss both historical and emerging functional genomics approaches and their impact on the cancer research landscape.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3057
Author(s):  
Lukasz Kuryk ◽  
Laura Bertinato ◽  
Monika Staniszewska ◽  
Katarzyna Pancer ◽  
Magdalena Wieczorek ◽  
...  

In this review, we discuss the use of oncolytic viruses and checkpoint inhibitors in cancer immunotherapy in melanoma, with a particular focus on combinatory therapies. Oncolytic viruses are promising and novel anti-cancer agents, currently under investigation in many clinical trials both as monotherapy and in combination with other therapeutics. They have shown the ability to exhibit synergistic anticancer activity with checkpoint inhibitors, chemotherapy, radiotherapy. A coupling between oncolytic viruses and checkpoint inhibitors is a well-accepted strategy for future cancer therapies. However, eradicating advanced cancers and tailoring the immune response for complete tumor clearance is an ongoing problem. Despite current advances in cancer research, monotherapy has shown limited efficacy against solid tumors. Therefore, current improvements in virus targeting, genetic modification, enhanced immunogenicity, improved oncolytic properties and combination strategies have a potential to widen the applications of immuno-oncology (IO) in cancer treatment. Here, we summarize the strategy of combinatory therapy with an oncolytic vector to combat melanoma and highlight the need to optimize current practices and improve clinical outcomes.


2021 ◽  
Vol 22 (13) ◽  
pp. 6744
Author(s):  
Fabrice Tolle ◽  
Viktor Umansky ◽  
Jochen Utikal ◽  
Stephanie Kreis ◽  
Sabrina Bréchard

Neutrophils—once considered as simple killers of pathogens and unexciting for cancer research—are now acknowledged for their role in the process of tumorigenesis. Neutrophils are recruited to the tumor microenvironment where they turn into tumor-associated neutrophils (TANs), and are able to initiate and promote tumor progression and metastasis. Conversely, anti-tumorigenic properties of neutrophils have been documented, highlighting the versatile nature and high pleiotropic plasticity of these polymorphonuclear leukocytes (PMN-L). Here, we dissect the ambivalent roles of TANs in cancer and focus on selected functional aspects that could be therapeutic targets. Indeed, the critical point of targeting TAN functions lies in the fact that an immunosuppressive state could be induced, resulting in unwanted side effects. A deeper knowledge of the mechanisms linked to diverse TAN functions in different cancer types is necessary to define appropriate therapeutic strategies that are able to induce and maintain an anti-tumor microenvironment.


2009 ◽  
Vol 27 (5) ◽  
pp. 812-826 ◽  
Author(s):  
Eric Winer ◽  
Julie Gralow ◽  
Lisa Diller ◽  
Beth Karlan ◽  
Patrick Loehrer ◽  
...  

A MESSAGE FROM ASCO'S PRESIDENTNearly 40 years ago, President Richard Nixon signed the National Cancer Act, mobilizing the country's resources to make the “conquest of cancer a national crusade.” That declaration led to a major investment in cancer research that has significantly improved cancer prevention, treatment, and survival. As a result, two thirds of people diagnosed with cancer today will live at least 5 years after diagnosis, compared with just half in the 1970s. In addition, there are now more than 12 million cancer survivors in the United States—up from 3 million in 1971. Scientifically, we have never been in a better position to advance cancer treatment. Basic scientific research, fueled in recent years by the tools of molecular biology, has generated unprecedented knowledge of cancer development. We now understand many of the cellular pathways that can lead to cancer. We have learned how to develop drugs that block those pathways; increasingly, we know how to personalize therapy to the unique genetics of the tumor and the patient. Yet in 2008, 1.4 million people in the United States will still be diagnosed with cancer, and more than half a million will die as a result of the disease. Some cancers remain stubbornly resistant to treatment, whereas others cannot be detected until they are in their advanced, less curable stages. Biologically, the cancer cell is notoriously wily; each time we throw an obstacle in its path, it finds an alternate route that must then be blocked. To translate our growing basic science knowledge into better treatments for patients, a new national commitment to cancer research is urgently needed. However, funding for cancer research has stagnated. The budgets of the National Institutes of Health and the National Cancer Institute have failed to keep pace with inflation, declining up to 13% in real terms since 2004. Tighter budgets reduce incentives to support high-risk research that could have the largest payoffs. The most significant clinical research is conducted increasingly overseas. In addition, talented young physicians in the United States, seeing less opportunity in the field of oncology, are choosing other specialties instead. Although greater investment in research is critical, the need for new therapies is only part of the challenge. Far too many people in the United States lack access to the treatments that already exist, leading to unnecessary suffering and death. Uninsured cancer patients are significantly more likely to die than those with insurance, racial disparities in cancer incidence and mortality remain stark, and even insured patients struggle to keep up with the rapidly rising cost of cancer therapies. As this annual American Society of Clinical Oncology report of the major cancer research advances during the last year demonstrates, we are making important progress against cancer. But sound public policies are essential to accelerate that progress. In 2009, we have an opportunity to reinvest in cancer research, and to support policies that will help ensure that every individual in the United States receives potentially life-saving cancer prevention, early detection, and treatment. Sincerely, Richard L. Schilsky, MD President American Society of Clinical Oncology


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Susann Haehnel ◽  
Kristin Reiche ◽  
Dennis Loeffler ◽  
Andreas Horn ◽  
Conny Blumert ◽  
...  

AbstractCancer research requires models closely resembling the tumor in the patient. Human tissue cultures can overcome interspecies limitations of animal models or the loss of tissue architecture in in vitro models. However, analysis of tissue slices is often limited to histology. Here, we demonstrate that slices are also suitable for whole transcriptome sequencing and present a method for automated histochemistry of whole slices. Tumor and peritumoral tissue from a patient with glioblastoma was processed to slice cultures, which were treated with standard therapy including temozolomide and X-irradiation. Then, RNA sequencing and automated histochemistry were performed. RNA sequencing was successfully accomplished with a sequencing depth of 243 to 368 x 106 reads per sample. Comparing tumor and peritumoral tissue, we identified 1888 genes significantly downregulated and 2382 genes upregulated in tumor. Treatment significantly downregulated 2017 genes, whereas 1399 genes were upregulated. Pathway analysis revealed changes in the expression profile of treated glioblastoma tissue pointing towards downregulated proliferation. This was confirmed by automated analysis of whole tissue slices stained for Ki67. In conclusion, we demonstrate that RNA sequencing of tissue slices is possible and that histochemical analysis of whole tissue slices can be automated which increases the usability of this preclinical model.


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