Treatment Of Difficult Diseases Research Articles

Nanophotonic Enhanced Chiral Sensing and Its Biomedical Applications.

Chiral sensing is crucial in the fields of biology and the pharmaceutical industry. Many naturally occurring biomolecules, i.e., amino acids, sugars, and nucleotides, are inherently chiral. Their enantiomers are strongly associated with the pharmacological effects of chiral drugs. Owing to the extremely weak chiral light-matter interactions, chiral sensing at an optical frequency is challenging, especially when trace amounts of molecules are involved. The nanophotonic platform allows for a stronger interaction between the chiral molecules and light to enhance chiral sensing. Here, we review the recent progress in nanophotonic-enhanced chiral sensing, with a focus on the superchiral near-field and enhanced circular dichroism (CD) spectroscopy generated in both the dielectric and in plasmonic structures. In addition, the recent applications of chiral sensing in biomedical fields are discussed, including the detection and treatment of difficult diseases, i.e., Alzheimer's disease, diabetes, and cancer.

Carotid Body Tumor, Cardiac Paraganglioma, Adrenal Pheochromocytoma: A Contest with Hypercatecholamineemia

This patient was an elderly man with left carotid body tumor, cardiac paraganglioma and right adrenal pheochromocytoma at the same time. This is a rare case with a complex condition, and the diagnosis and treatment were difficult. After two rounds of discussion in the multidisciplinary team, our hospital has successively removed the lesions of the heart and the right adrenal, and the patient was discharged smoothly after the operations. The diagnosis and treatment of this patient reflects the significance of the multidisciplinary team on the diagnosis and treatment of difficult diseases.

Exploration of five-element acupuncture that focused on "treating spirit" in diagnosis and treatment of difficult diseases

This paper focused on "treating spirit" in acupuncture based on the problems and needs in the diagnosis and treatment of difficult diseases, and discussed the diagnosis and treatment of difficult diseases with five-element acupuncture from six aspects: ① integration of soma and spirit in TCM, give top priority to "treating spirit" in acupuncture treatment; ②inadequate understanding of "treating spirit" in conventional acupuncture clinic; ③five-pattern personality and "treating spirit" with acupuncture; ④ five-element acupuncture and holism of correspondence between man and universe; ⑤searching for the primary cause of disease in treatment and motivating self-healing power by five-element acupuncture; ⑥advantages and methods of five-element acupuncture in "treating spirit". It shows that five-element acupuncture can be used to inspire new ideas of diagnosis and treatment of difficult diseases in acupuncture clinic.

Abstract 281: Novel nucleic acid constructs and formulations for treatment of bladder cancer and malignant ascites

Abstract Nucleic acid-based therapeutics offer significant promise in treatment of difficult diseases by providing high sequence specificity against target genes including “non-druggable targets”. Different nucleic acid constructs, single-stranded antisense oligonucleotides, microRNA mimetics, miRNA-specific antagomirs (AntimiR), and double-stranded short-interfering RNAs (siRNAs), provide diverse therapeutic platforms to access targets in treatment of cancer and other diseases. Single-stranded oligonucleotides require additional modifications for increased serum stability, nuclease resistance, and to minimize immune response. Conformationally restricted nucleotide (CRN)-substituted AntimiRs targeting miR-21 and miR-122 demonstrated significant improvement in hybridization affinity with a concomitant increase in potency. A CRN-substituted AntimiR targeting microRNA-122 dosed at up to 50 mg/kg/day over three consecutive days led to a dose-dependent effect on de-repression of downstream liver-specific target genes, Aldolase A (AldoA), Glycogen Synthase I (GYS1) and Solute Carrier Family 7 member 1 (SLC7A1). This CRN-modified AntimiR produced up to a 5-fold increase in AldoA mRNA while demonstrating a good tolerability profile with no body weight changes and normal serum chemistry. Development of therapeutic siRNA constructs can be hampered by off-target effects and cytokine induction. Substitution of unlocked nucleobase analogs (UNAs) at specific positions in the passenger and guide strands of siRNA confers high specificity with minimal to no off-target activity. UsiRNAs were successfully delivered to bladder or abdominal tumors when encapsulated in DiLA2- or SMARTICLES®-derived liposomes. DiLA2−encapsulated polo-like kinase 1 (PLK1) UsiRNA demonstrated 95% mRNA reduction and up to 70-fold tumor growth inhibition in a bladder cancer orthotopic mouse model and 40-70% mRNA inhibition and ∼80% reduction in tumor-specific bioluminescence in a malignant ascites mouse model following intravesical or intraperitoneal dosing, respectively. In an orthotopic liver tumor animal model, liposomal encapsulated miRNA mimetics provided ∼80% reduction in tumors compared to buffer control. Combinations of formulations and construct capitalize on the advantages of nucleic acid-based therapeutics for precise targeting and flexible delivery to challenging drug targets in cancer and other indications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 281. doi:1538-7445.AM2012-281