The potential of monoclonal antibodies for colorectal cancer therapy.

Conventional chemotherapy has significant limitations for colorectal cancer (CRC) treatment, especially those who have developed metastatic recurrence CRC. A growing number of studies have investigated the potential use of monoclonal antibodies (mAbs) for CRC therapy. mAbs showing clinical benefits for CRC, making the treatment more selective with lower side effects without significant immunogenicity. In addition, recent advancements in antibody engineering strategies and the development of bifunctional or even trifunctional drugs have helped to overcome heterogeneity as the main challenge in cancer treatment. The current review discusses advances in applying mAbs for CRC therapy alone, combined, or with small molecules.

MicroRNAs and their Implications in CD4+ T-cells, Oligodendrocytes and Dendritic Cells in Multiple Sclerosis Pathogenesis.

MicroRNAs (miRNAs) have been established as key players in various biological processes regulating differentiation, proliferation, inflammation, and autoimmune disorders. Emerging evidence suggests the critical role of miRNAs in the pathogenesis of multiple sclerosis (MS). Here, we provide a comprehensive overview of miRNAs, which are differentially expressed in MS patients or experimental autoimmune encephalomyelitis (EAE) mice and contribute to MS pathogenesis through regulating diverse pathways, including CD4+ T cells proliferation, differentiation, and activation in three subtypes of CD4+ T cells, including Th1, Th17 and regulatory T cells (Tregs). Moreover, the regulation of oligodendrocyte precursor cells (OPC) differentiation as a crucial player in MS pathogenesis is also described. Our literature research showed that miR-223 could affect different pathways involved in MS pathogenesis, such as promoting Th1 differentiation, activating the M2 phenotype of myeloid cells, and clearing myelin debris. MiR-223 was also identified as a potential biomarker, distinguishing relapsing-remitting multiple sclerosis (RRMS) from progressive multiple sclerosis (PMS), and thus, it may serve as an attractive target for further investigations. Our overview provides novel potential therapeutic targets for the treatment and new insights into miRNAs' role in MS pathogenesis.

Angioregulatory microRNAs in breast cancer: Molecular mechanistic basis and implications for therapeutic strategies.

Background: Cancer-associated angiogenesis is a fundamental process in tumor growth and metastasis. A variety of signaling regulators and pathways contribute to establish neovascularization, among them as small endogenous non-coding RNAs, microRNAs (miRNAs) play prominent dual regulatory function in breast cancer (BC) angiogenesis. Aim of Review: This review aims at describing the current state-of-the-art in BC angiogenesis-mediated by angioregulatory miRNAs, and an overview of miRNAs dysregulation association with the anti-angiogenic response in addition to potential clinical application of miRNAs-based therapeutics. Key Scientific Concepts of Review: Angioregulatory miRNA-target gene interaction is not only involved in sprouting vessels of breast tumors but also, trans-differentiation of BC cells to endothelial cells (ECs) in a process termed vasculogenic mimicry. Using canonical and non-canonical angiogenesis pathways, the tumor cell employs the oncogenic characteristics such as miRNAs dysregulation to increase survival, proliferation, oxygen and nutrient supply, and treatment resistance. Angioregulatory miRNAs in BC cells and their microenvironment have therapeutic potential in cancer treatment. Although, miRNAs dysregulation can serve as tumor biomarker nevertheless, due to the association of miRNAs dysregulation with anti-angiogenic resistant phenotype, clinical benefits of anti-angiogenic therapy might be challenging in BC. Hence, unveiling the molecular mechanism underlying angioregulatory miRNAs sparked a booming interest in finding new treatment strategies such as miRNA-based therapies in BC.

Downregulation of serum miR-106b: a potential biomarker for Alzheimer disease.

Analysis of miRNAs has a strong potential for the identification of novel prognostic or predictive biomarkers in the serum of AD patients. In this study, we investigated the serum levels of miR-106b as a diagnostic biomarker for AD and evaluate its predictive value for therapeutic response to the drug rivastigmine. Patients were divided into either responding (n = 33) or non-responding (n = 23) groups according to rivastigmine treatment and to Mini-Mental State Exam score. The serum concentrations of miR-106b were measured with real-time PCR. Here, we found that miR-106b was significantly down-regulated in the serum samples of AD patients compared with those of controls (p < .001). ROC results showed a specificity of 62% and a sensitivity of 94%. The serum values of miR-106b tended to be positively associated with the therapeutic response but were not significant (p = .15). Taken together, detection of serum miR-106b might be a promising serum biomarker for early diagnosis of AD.

Potential microRNA-related targets in clearance pathways of amyloid-ß: novel therapeutic approach for the treatment of Alzheimer's disease.

Imbalance between amyloid-beta (Aß) peptide synthesis and clearance results in Aß deregulation. Failure to clear these peptides appears to cause the development of Alzheimer's disease (AD). In recent years, microRNAs have become established key regulators of biological processes that relate among others to the development and progression of neurodegenerative diseases, such as AD. This review article gives an overview on microRNAs that are involved in the Aß cascade and discusses their inhibitory impact on their target mRNAs whose products participate in Aß clearance. Understanding of the mechanism of microRNA in the associated signal pathways could identify novel therapeutic targets for the treatment of AD.

MicroRNA expression studies: challenge of selecting reliable reference controls for data normalization.

Accurate determination of microRNA expression levels is a prerequisite in using these small non-coding RNA molecules as novel biomarkers in disease diagnosis and prognosis. Quantitative PCR is the method of choice for measuring the expression levels of microRNAs. However, a major obstacle that affects the reliability of results is the lack of validated reference controls for data normalization. Various non-coding RNAs have previously been used as reference controls, but their use may lead to variations and lack of comparability of microRNA data among the studies. Despite the growing number of studies investigating microRNA profiles to discriminate between healthy and disease stages, robust reference controls for data normalization have so far not been established. In the present article, we provide an overview of different reference controls used in various diseases, and highlight the urgent need for the identification of suitable reference controls to produce reliable data. Our analysis shows, among others, that RNU6 is not an ideal normalizer in studies using patient material from different diseases. Finally, our article tries to disclose the challenges to find a reference control which is uniformly and stably expressed across all body tissues, fluids, and diseases.

Recent advances in applying nanotechnologies for cancer immunotherapy.

Cancer immunotherapy aimed at boosting cancer-specific immunoresponses to eradicate tumor cells has evolved as a new treatment modality. Nanoparticles incorporating antigens and immunomodulatory agents can activate immune cells and modulate the tumor microenvironment to enhance anti-tumor immunity. The nanotechnology approach has been demonstrated to be superior to standard formulations in in-vivo settings. In this article, we focus on recent advances made within the last 5 years in nanoparticle-based cancer immunotherapy, including peptide- and nucleic acid-based nanovaccines, nanomedicines containing an immunoadjuvant to activate anti-tumor immunity, nanoparticle delivery of immune checkpoint inhibitors and the combination of the above approaches. Encouraging results and new emerging nanotechnologies in drug delivery promise the continuous growth of this field and ultimately clinical translation of enhanced immunotherapy of cancer.