Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead,... more
Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead, ASD is more frequently due to many polygenic contributing factors interacting with each other, combined with the epigenetic effects of diet, lifestyle, and environment. One limitation of genomics has been identifying ways of responding to each identified gene variant to translate the information to something clinically useful. This paper will illustrate how understanding the function of a gene and the effects of a reported variant on a molecular level can be used to develop actionable and targeted potential interventions for a gene variant or combinations of variants. For illustrative purposes, this communication highlights a specific genomic variant, SHANK3. The steps involved in developing molecularly genomically targeted actionable interventions will be demonstrated. Cases will be shared to support the efficacy of this strategy and to show how clinicians utilized these targeted interventions to improve ASD-related symptoms significantly. The presented approach demonstrates the utility of genomics as a part of clinical decision-making.
The detection of breast cancer in early stages is a major factor in the reduction of patient mortality. Although mammography is an effective imaging tool in diagnosis of breast cancer, it is not without some limitations. Other imaging... more
The detection of breast cancer in early stages is a major factor in the reduction of patient mortality. Although mammography is an effective imaging tool in diagnosis of breast cancer, it is not without some limitations. Other imaging modalities such as US, MRI and CT initiated to increase the diagnostic accuracy of mammography, have strengths and weaknesses in terms of sensitivity, specificity, spatial and temporal resolution, contrast and cost. The application of nuclear medicine techniques to study patients with breast cancer has recently raised its profile, particularly in the investigation of indeterminate mammographic lesions and for overcoming limitations of other imaging techniques. Currently, for increasing sensitivity and specificity of nuclear medicine techniques, researchers are studying on targeted molecular imaging methods. The recent advances in molecular and cellular biology have facilitated the discovery of novel molecular targets on breast tumor cells such as key molecules involved in proliferation, differentiation, cell death and apoptosis, angiogenesis and metastasis. In this paper, the history of radioimmunodetection of breast cancer as a targeting molcular imaging method will be reviwed.
Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized therapy and regular follow-up are the keys to... more
Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized therapy and regular follow-up are the keys to a successful outcome. Cancer stem cells (CSCs) are the leading power behind tumor growth, with the ability of self-renewal, metastasis, and resistance to conventional chemotherapy. The fast-developing CSC field with robust genome-wide screening methods has found a platform for establishing more reliable therapies to target tumor-initiating cell populations. However, the high heterogeneity of the CSCs in BC disease remains a large issue. Therefore, in the present review, we discuss the various types of bladder CSC heterogeneity, important regulatory pathways, roles in tumor progression and tumorigenesis, and the experimental culture models. Finally, we describe the current stem cell-based therapies for BC disease.
Background: HIV-1 Tat is essential for HIV replication and is also a well-known neurotoxic factor causing HIV-associated neurocognitive disorder (HAND). Currently, combined antiretroviral therapy targeting HIV reverse transcriptase or... more
Background: HIV-1 Tat is essential for HIV replication and is also a well-known neurotoxic factor causing HIV-associated neurocognitive disorder (HAND). Currently, combined antiretroviral therapy targeting HIV reverse transcriptase or protease cannot prevent the production of early viral proteins, especially Tat, once HIV infection has been established. HIV-infected macrophages and glial cells in the brain still release Tat into the extracellular space where it can exert direct and indirect neurotoxicity. Therefore, stable production of anti-Tat antibodies in the brain would neutralize HIV-1 Tat and thus provide an effective approach to protect neurons. Methods: We constructed a humanized anti-Tat Hutat2:Fc fusion protein with the goal of antagonizing HIV-1 Tat and delivered the gene into cell lines and primary human monocyte-derived macrophages (hMDM) by an HIV-based lentiviral vector. The function of the anti-Tat Hutat2:Fc fusion protein and the potential side effects of lentiviral vector-mediated gene transfer were evaluated in vitro. Results: Our study demonstrated that HIV-1-based lentiviral vector-mediated gene transduction resulted in a high-level, stable expression of anti-HIV-1 Tat Hutat2:Fc in human neuronal and monocytic cell lines, as well as in primary hMDM. Hutat2:Fc was detectable in both cells and supernatants and continued to accumulate to high levels within the supernatant. Hutat2:Fc protected mouse cortical neurons against HIV-1 Tat86-induced neurotoxicity. In addition, both secreted Hutat2:Fc and transduced hMDM led to reducing HIV-1BaL viral replication in human macrophages. Moreover, lentiviral vector-based gene introduction did not result in any significant changes in cytomorphology and cell viability. Although the expression of IL8, STAT1, and IDO1 genes was up-regulated in transduced hMDM, such alternation in gene expression did not affect the neuroprotective effect of Hutat2:Fc. Conclusions: Our study demonstrated that lentivirus-mediated gene transfer could efficiently deliver the Hutat2:Fc gene into primary hMDM and does not lead to any significant changes in hMDM immune-activation. The neuroprotective and HIV-1 suppressive effects produced by Hutat2:Fc were comparable to that of a full-length anti-Tat antibody. This study provides the foundation and insights for future research on the potential use of Hutat2:Fc as a novel gene therapy approach for HAND through utilizing monocytes/macrophages, which naturally cross the blood-brain barrier, for gene delivery.
