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Progress in Molecular Biology and Translational Science

Ellen Shrock, Marc Güell
CRISPR-Cas9 has revolutionized the generation of transgenic animals. This system has demonstrated an unprecedented efficiency, multiplexability, and ease of use, thereby reducing the time and cost required for genome editing and enabling the production of animals with more extensive genetic modifications. It has also been shown to be applicable to a wide variety of animals, from early-branching metazoans to primates. Genome-wide screens in model organisms have been performed, accurate models of human diseases have been constructed, and potential therapies have been tested and validated in animal models...
2017: Progress in Molecular Biology and Translational Science
Takuro Horii, Izuho Hatada
Haploidy is a useful feature for the study of gene function because disruption of one allele in haploid cells, which contain only a single set of chromosomes, can cause loss-of-function phenotypes. Recent success in generating haploid embryonic stem (ES) cells from several mammalian species, including human, provides a new platform for simple genetic manipulation of the mammalian genome. The genome-editing potential of the CRISPR/Cas system is enhanced by the use of haploid ES cells. For example, CRISPR/Cas has been used for high-efficiency generation of multiple knockouts and knockins in haploid ES cells, with potential application in genome-wide screening...
2017: Progress in Molecular Biology and Translational Science
John T Poirier
CRISPR-Cas9 technology has revolutionized large-scale functional genomic screening in mammalian cell-culture systems. Due in part to optimized lentiviral delivery vectors; it is now possible to perform CRISPR-Cas9 screens in animals in order to study biological processes in the context of a whole organism and within more physiologically relevant environment. This chapter focuses primarily on mouse models of human cancers; viral vectors used for simultaneous tumor initiation and genome editing and sgRNA library design considerations...
2017: Progress in Molecular Biology and Translational Science
Michael Kosicki, Sandeep S Rajan, Flaminia C Lorenzetti, Hans H Wandall, Yoshiki Narimatsu, Emmanouil Metzakopian, Eric P Bennett
The introduction of CRISPR/Cas9 gene editing in mammalian cells is a scientific breakthrough, which has greatly affected basic research and gene therapy. The simplicity and general access to CRISPR/Cas9 reagents has in an unprecedented manner "democratized" gene targeting in biomedical research, enabling genetic engineering of any gene in any cell, tissue, organ, and organism. The ability for fast, precise, and efficient profiling of the double-stranded break induced insertions and deletions (indels), mediated by any of the available programmable nucleases, is paramount to any given gene targeting approach...
2017: Progress in Molecular Biology and Translational Science
Marta Martinez-Lage, Raúl Torres-Ruiz, Sandra Rodriguez-Perales
The CRISPR/Cas9 system development has revolutionized the field of genome engineering through the efficient creation of targeted breaks in the DNA of almost any organism and cell type, opening an avenue for a wide range of applications in biomedical research and medicine. Apart from gene edition through knock-in or knock-out approaches, CRISPR/Cas9 technology has been used for many other purposes, including regulation of endogenous gene expression, epigenome editing, live-cell imaging of chromosomal loci, edition of RNA and high-throughput screening...
2017: Progress in Molecular Biology and Translational Science
Juan C Ramirez
A few years ago, we assisted in the demonstration for the first time of the revolutionary idea of a type of adaptive-immune system in the bacteria kingdom. This system, named CRISPR, and variants engineered in the lab, have been demonstrated as functional with extremely high frequency and fidelity in almost all eukaryotic cells studied to date. The capabilities of this RNA-guided nuclease have added to the interest that was announced with the advent of previous technologies for genome editing tools, such as ZFN and TALEN...
2017: Progress in Molecular Biology and Translational Science
Wenyuan Han, Qunxin She
CRISPR research is a very young research field since it was only 10years ago when the system was found to confer antiviral defense. Nevertheless, there has been an explosion of publications in CRISPR research in the past 5years. The research was started with the comparative genomics of microbial genomes early this century, which revealed the prevalence of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) in bacteria and archaea. Series of hypotheses were made based on bioinformatics analyses and tested experimentally within a few years after the CRISPR acronym was coined...
2017: Progress in Molecular Biology and Translational Science
(no author information available yet)
No abstract text is available yet for this article.
2017: Progress in Molecular Biology and Translational Science
Ramadevi Subramani, Rajkumar Lakshmanaswamy
Breast cancer is the most commonly diagnosed type of cancer among women worldwide. The majority of breast cancers are sporadic and the etiology is not well understood. Several factors have been attributed to altering the risk of breast cancer. A full-term pregnancy is a crucial factor in altering the risk. Early full-term pregnancy has been shown to reduce the lifetime risk of breast cancer, while a later first full-term pregnancy increases breast cancer risk. Epidemiological and experimental data demonstrate that spontaneous or induced abortions do not significantly alter the risk of breast cancer...
2017: Progress in Molecular Biology and Translational Science
Randi Ryan, Ossama Tawfik, Roy A Jensen, Shrikant Anant
The presentation and treatment of ductal carcinoma in situ (DCIS) has changed substantially over the years. While previously an incidental pathologic finding in more advanced, palpable tumors, the institution of screening mammography has repositioned this disease entity as one largely diagnosed as a non-palpable lesion, often prior to any invasive disease. As DCIS is a precursor to invasive carcinoma, evolution in the approach to treatment has followed in the footsteps of that for invasive disease, including breast conservation therapy, adjuvant radiation, and use of antihormonal therapy...
2017: Progress in Molecular Biology and Translational Science
Ramadevi Subramani, Rajkumar Lakshmanaswamy
Complementary and alternative medicine (CAM) has been in use among cancer patients for a long time. There are several types of CAM that are practiced in various parts of the world. For example, traditional medicinal practices followed in India and China are frequently used by cancer patients. CAM is broadly classified into five different categories: (1) traditional medicines, (2) mind-body interventions, (3) biology-based practices, (4) manipulative body-based practices, and (5) energy medicine. In this review, we have compiled data from the available literature regarding CAM use in breast cancer patients...
2017: Progress in Molecular Biology and Translational Science
Sridhar Mani
Breast carcinogenesis and/or cancer growth and/or drug sensitivity has a multifactorial etiology-perhaps the least well-characterized aspect being that of the distant environmental influences, namely, the microbiota that inhabit humans. For the purposes of this chapter, and to keep the subject matter well defined, microbiota is defined as bacterial microbes only. In this chapter, the pathways that lead to priming of breast cancer and/or the maintenance of a malignant state and/or influences on drug sensitivity via bacterial influences will be identified and described...
2017: Progress in Molecular Biology and Translational Science
Jiang-Jiang Qin, Wei Wang, Ruiwen Zhang
Advanced breast cancer, especially advanced triple-negative breast cancer, is typically more aggressive and more difficult to treat than other breast cancer phenotypes. There is currently no curable option for breast cancer patients with advanced diseases, highlighting the urgent need for novel treatment strategies. We have recently discovered that the nuclear factor of activated T cells 1 (NFAT1) activates the murine double minute 2 (MDM2) oncogene. Both MDM2 and NFAT1 are overexpressed and constitutively activated in breast cancer, particularly in advanced breast cancer, and contribute to its initiation, progression, and metastasis...
2017: Progress in Molecular Biology and Translational Science
Kumaraguruparan Ramasamy, Cathy Samayoa, Naveen Krishnegowda, Rajeshwar R Tekmal
Breast cancer is one of the most common cancers in the world. The majority of breast cancers express estrogen receptor (ER)α, and endocrine therapy is the primary therapeutic approach to treat ER positive breast cancers. However, developing resistance and side effects are common events of these therapeutic strategies. Recent studies have evaluated the role of ERs sub types and demonstrated that ERα is a tumorigenic and ERβ functions as a tumor suppressor. In recent years, preclinical studies focused on the use of natural and synthetic ERβ agonists to treat wide varieties of cancers, including breast cancer...
2017: Progress in Molecular Biology and Translational Science
Sushmita Bose Nandy, Rajkumar Lakshmanaswamy
Decades of cancer research have led to substantial progress in the treatment of primary breast cancers. Despite of the advancement in this field, treating a metastatic disease has remained a mammoth task. One of the possible theories explaining metastatic disease involves the cancer stem cells (CSCs). CSCs have been shown to be an integral part of solid tumors. The process of metastasis involves the fine orchestration between CSCs and other microenvironmental factors. This chapter will provide an overview about the process of metastasis and the interactive role of CSCs with the components of the microenvironment in each phase of the metastatic cascade...
2017: Progress in Molecular Biology and Translational Science
Jeronay King, Hina Mir, Shailesh Singh
Breast cancer touches women's life worldwide. Expected outcome is not achieved due to molecular heterogeneity and complex biology despite substantial advancement in diagnosis, prevention and treatment of breast cancer. Patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) positive tumors receive hormone ablation and Her2 directed therapy. While patients diagnosed with triple-negative breast cancer receive chemotherapy in both the early and advanced stages...
2017: Progress in Molecular Biology and Translational Science
Stella Winters, Charmaine Martin, Daniel Murphy, Navkiran K Shokar
Globally, breast cancer is both the most commonly occurring cancer and the commonest cause of cancer death among women. Available data suggest that incidence and mortality in high-resource countries has been declining whereas incidence and mortality in low-resource countries has been increasing. This pattern is likely to be due to changing risk factor profiles and differences in access to breast cancer early detection and treatment. Risk factors for breast cancer include increasing age, race, menarche history, breast characteristics, reproductive patterns, hormone use, alcohol use, tobacco use, diet, physical activity, and body habitus...
2017: Progress in Molecular Biology and Translational Science
Giuseppe Legname, Silvia Vanni
No abstract text is available yet for this article.
2017: Progress in Molecular Biology and Translational Science
Ivana Biljan, Gregor Ilc, Janez Plavec
Prion diseases or transmissible spongiform encephalopathies constitute a group of fatal neurodegenerative diseases that can be of sporadic, genetic, or acquired origin. The central molecular event of prion diseases is the conformational conversion of the physiological cellular prion protein, PrP(C), into a disease-associated form known as prion or PrP(Sc). Spontaneous generation of prions in genetic prion diseases is caused by mutations in the human prion protein gene (PRNP). Understanding of the earliest conformational changes during misfolding of PrP(C) in genetic forms of prion diseases may benefit from detailed structural characterization of various human (Hu) PrP variants...
2017: Progress in Molecular Biology and Translational Science
Daniela Sarnataro, Anna Pepe, Chiara Zurzolo
Cellular prion protein (PrP(C)) is a mammalian glycoprotein which is usually found anchored to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. The precise function of PrP(C) remains elusive but may depend upon its cellular localization. PrP(C) misfolds to a pathogenic isoform PrP(Sc), the causative agent of neurodegenerative prion diseases. Nonetheless some forms of prion disease develop in the apparent absence of infectious PrP(Sc), suggesting that molecular species of PrP distinct from PrP(Sc) may represent the primary neurotoxic culprits...
2017: Progress in Molecular Biology and Translational Science
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