Therapies In Clinical Settings Research Articles

The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer.

Chemoresistance is one of the major hurdles in the treatment of breast cancer, which limits the effect of both targeted and conventional therapies in clinical settings. Therefore, understanding the mechanisms underpinning resistance is paramount for developing strategies to circumvent resistance in breast cancer patients. Several published reports have indicated that lncRNAs play a dynamic role in the regulation of both intrinsic and acquired chemoresistance through a variety of mechanisms that endow cells with a drug-resistant phenotype. Although a number of lncRNAs have been implicated in chemoresistance of breast cancer, their mechanistic roles have not been systematically reviewed. Thus, here we present a detailed review on the latest research findings and discoveries on the mechanisms of acquisition of chemoresistance in breast cancer related to lncRNAs, and how lncRNAs take part in various cancer signalling pathways involved in breast cancer cells. Knowledge obtained from this review could assist in the development of new strategies to avoid or reverse drug resistance in breast cancer chemotherapy.

MicroRNA as Regulators of Cancer Stem Cells and Chemoresistance in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The development of resistance to anti-cancer treatment is one of the major challenges in the treatment of CRC, which limits the efficacy of both conventional and targeted therapies in clinical settings. Understanding the mechanisms underpinning resistances is therefore critical in developing novel agents to reverse drug resistance and for more specific targeted treatments. Accumulating studies have reported that microRNAs (miRNAs) are key players in the regulation of cancer cells with intrinsic/acquired drug resistance through varied mechanisms that endow cells with a drug-resistant phenotype. miRNAs have been evolved in the regulation of chemoresistance to various CRC treatments and the stemness of CRC stem cells (CRSCs), sequentially modulating the sensitivity of CRC cells to anti-cancer treatments. Targeting miRNAs may be a novel strategy for eradicating CRSCs, re-sensitizing drug-resistant cells to anti-cancer agents, improving drug efficiency and developing novel biological agents for CRC treatment. This paper highlights the role of miRNAs in the regulation of chemoresistance and CRSCs in CRC, with focus on the mechanisms underlying how miRNAs alter CRSCs fate, and the process of epithelial-to-mesenchymal transition, cell cycle and apoptosis in CRC cells.

The Need for a Theoretical Framework of Social Functioning to Optimize Targeted Therapies in Psychiatric Disorders

Oxytocin (OT) matters for social functioning, and optimal evaluations of therapeutic efficacy matter for individuals with psychiatric and neurodevelopmental disorders. Recently, Guastella and Hickie (1), experts in the field of autism therapeutics, provided a comprehensive review of the potential of OT for improving social cognition in patients with autism spectrum disorder (ASD) and emphasized the need for better approaches to evaluate OT therapies in clinical settings. The ancient 500 million-year-old OT system has undergone tremendous physiologic transformations in neuronal morphology, axonal projections, and receptor distribution in the brain to shape species-specific social features, such as maternal motivation, pair bonding, and social learning (2). By using pharmacologic approaches and transgenic mice with mutations in the genes encoding OT or its receptor, researchers refined the role of OT in social information processing and social recognition (3). In recent decades, OT has become the sweetheart of social neuroscientists because of its effects on social behavior and its potential for enhancing social skills in individuals with psychiatric disorders. Long-term administration of OT to individuals with ASD was recently shown to be safe and to increase social reciprocity (4,5) and eye gaze (4). These behavioral improvements were associated with increased functional connectivity between anterior cingulate cortex and dorsomedial prefrontal cortex (4), which is known to be significantly altered in ASD. These promising findings are in agreement with the recent discovery that long-term intranasal administration of OT restored social behavior in a mouse model of autism (6). The key challenge in intranasal OT research is to translate optimistic research findings into potential therapies yielding sustainable improvements in social functioning in individuals with ASD.

Targeted therapies of cancer: Angiogenesis inhibition seems not enough

The therapeutic potential of targeting tumor endothelium to induce tumor regression is now widely recognized. Tumors obtain their blood supply by the formation of new vasculature and the incorporation of pre-existent vessels. Since anti-angiogenic therapy prevents formation of neovasculature, vessels in more matured stages are not affected by such therapies. Therefore, additional vascular targeting therapy, which aim at regression of existent tumor vasculature, seems an attractive approach to effectively deprive tumors from blood supply. In this review we present an overview of different strategies to target tumor endothelium. In addition, we discuss the pitfalls of anti-angiogenic therapies in clinical settings.

The Use of Analgesics in Birds, Reptiles, and Small Exotic Mammals

Exotic animal veterinarians have been prescribing analgesics for their patients for many years, but recently the recognition and alleviation of pain in these patients have become widely recognized as an essential component of clinical veterinary care. Misconceptions about the nature and significance of pain, difficulties in recognizing its severity, uncertainty as to the most appropriate therapies in clinical settings, and a fundamental lack of scientific data in exotic animals have hampered our understanding of pain management in these patients. To manage pain effectively in exotic animal patients, we must first be able to define and recognize pain in these animals. This article addresses some of these obstacles by discussing current knowledge concerning the recognition and management of pain in common pet exotic animal patients and by providing information regarding analgesic medications determined in other species, with the hopes of applying these fundamental understandings to our exotic animal patients.

Aerosol delivery of urocanic acid–modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings. Aerosol gene delivery as nonviral and noninvasive method for gene therapy may provide an alternative for a safer and more effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in previous study was used as a gene carrier. The efficiency of UAC carrier in lungs was confirmed, and the potential effects of the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model mice through the nose-only inhalation system developed by our group. Delivered UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell proliferation, and efficiently suppressed pathways important for tumor angiogenesis. In summary, results obtained by Western blot analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.