Cancer is the second leading cause of death by disease in the world. Chemotherapy is one of three major therapeutic methods for cancer treatment, but cancer cells gradually evolve resistance to chemotherapeutic reagents. For centuries, traditional Chinese medicine (TCM) was used to fight against cancer. In recent years, a number of effective component mechanisms of TCM have been increasingly illuminated. As we know, chemical structures of reagents decide or affect their activities on target pathways. Thus, we classified some antitumor-related TCM components reported in the last five years into thirteen groups by their chemical structures, such as, alkaloids, diterpenoids, triterpenes, sesquiterpenes, anthraquinones, benzoquinones, flavonoids, berbamines, xanthones, saponins, steroids, polysaccharides, and glycosides. In various cancer cell lines, these constituents target dozens of signaling pathways in vitro and in vivo. Among these components, there are three sets: i) mainly apoptosis-related groups, such as, alkaloids, diterpenoids, anthraquinones, berbamines, and xanthones, target pathways like the mitochondrial pathway, NF-κB pathway, p53 pathway and so on; ii) mainly proliferation, invasion and metastasis-related groups, such as, triterpenes, sesquiterpenes, polysaccharides, and glycosides, target pathways like the mTOR pathway, β-catenin pathway, ERK pathway and so on; iii) both apoptosis and proliferation, invasion and metastasis-related groups, such as benzoquinones, flavonoids, saponins, and steroids, target the pathways in i) and ii) synchronously. These will provide association information between TCM components and signaling pathways to promote studies on mechanisms of effective constituents, target drug development, and combinational chemotherapy. TCM could be alternative medicine for cancer treatment in the future.
Hepatocellular carcinoma (HCC) is a severe form of liver cancer that is found worldwide. Treatments such as liver transplantation and surgical resection and local-regional therapies such as transarterial chemoembolization have progressed considerably and play a prominent role in HCC management. After those treatments, though, systematic drug intervention is required to deal with tumor metastasis in its early stages and the high frequency of tumor recurrence and/or metastasis. The approval of sorafenib, an agent that targets receptor tyrosine kinases (RTKs), as the first effective drug for systemic treatment of HCC represents a milestone in the treatment of this disease. In addition to sorafenib, a number of agents that target various RTKs or intracellular signal transduction molecules, such as mTOR, are currently being investigated as monotherapy or combination therapy for HCC. This article reviews advances in the study of molecularly targeted agents to treat HCC.
We discuss the design of novel amphiphilic oligopeptides with hydrophobic and cationic amino acids to serve as models to understand peptide-DNA assembly. Biophysical and thermodynamic characterization of interaction of these amphiphilic peptides with plasmid DNA is presented. Peptides with at least +4 charges favor stable complex formation. Surface potential is dependent on the type of hydrophobic amino acid for a certain charge. Thermodynamically it is a spontaneous interaction between most of the peptides and plasmid DNA. Lys7 and Tyr peptides with +4/+5 charges indicate cooperative binding with pDNA without saturation of interaction while Val2-Gly-Lys4, Val-Gly-Lys5, and Phe-Gly-Lys5 lead to saturation of interaction indicating condensed pDNA within the range of N/Ps studied. We show that the biophysical properties of DNA-peptide complexes could be modulated by design and the peptides presented here could be used as building blocks for creating DNA-peptide complexes for various biomedical applications, mainly nucleic acid delivery.
This study aimed to clarify the expression profile of KL-6 mucin in intraductal papillary mucinous neoplasm (IPMN) and its relation to tumor malignancy. Expression of KL-6 mucin in 38 IPMNs (intraductal papillary mucinous adenoma (IPMA), 24 cases; minimally invasive intraductal papillary mucinous carcinoma (MI-IPMC), 8 cases; invasive carcinoma originating from IPMC (IC-IPMC), 6 cases) and 66 pancreatic ductal adenocarcinomas (PDACs) was evaluated immunohistochemically. IC-IPMCs and MI-IPMCs had positive staining of KL-6 mucin whereas 58% of IPMAs tested negative. Subcellular localization of KL-6 mucin varied among IPMNs whereas all of the PDAC had positive expression in the circumferential membrane and cytoplasm of cancer cells. IC-IPMCs and MI-IPMCs had a higher frequency of circumferential membrane and cytoplasmic localization of KL-6 mucin than did IPMAs. These results suggest that localization of KL-6 mucin could be used to predict the malignancy of IPMN.
Dexibuprofen, is a practically water-insoluble nonsterodial anti-inflammatory drug which has a better anti-inflammatory effect than ibuprofen. A mixed hydrotropic solubilization technique was applied in order to improve the aqueous solubility and dissolution rate of dexibuprofen. Nine formulae were prepared using different concentrations of hydrotropic agents (sodium citrate dihydrate and urea). The prepared formulae were inspected visually for color and odor. Hygroscopicity, micromeretic properties, solubility, and pH for 1% aqueous solutions were determined. In-vitro dissolution studies of the different prepared formulae were performed adopting the USP XXII dissolution method type I basket apparatus method. The prepared formulae were characterized by infrared (IR) spectroscopy and differential scanning calorimetry (DSC). The prepared formulae were a white color, odorless, slightly hygroscopic and exhibited good flow properties. Formulae containing higher amounts of hydrotropic agents exhibited an increase in the pH, solubility, rate and amount of dexibuprofen released from the dissolution medium. The highest dissolution rate was achieved from the F9 formula at drug:sodium citrate dihydrate:urea ratio (1:3:7.5). IR and DSC thermograph of dexibuprofen, hydrotropic agents and prepared formulae indicated the presence of intermolecular interaction between drug and hydrotropic agents which increased solubility and dissolution rate of drug, also, there is no chemical interaction confirming the stability of the drug with hydrotropic agents.
The purpose of this research was to develop a matrix-type transdermal therapeutic system containing drug heparin sodium with different ratios of hydrophilic polymeric systems by the solvent evaporation technique by using 30% (w/w) of PEG 400 LR to the dry polymer weight, incorporated as plasticizer. Different concentrations of oleic acid and isopropyl myristate were used to enhance the transdermal permeation of heparin sodium. The physicochemical compatibility of the drug and the polymers studied by differential scanning calorimetry and infrared spectroscopy suggested absence of any incompatibility. Formulated transdermal films were physically evaluated with regard to thickness, weight variation, drug content, flatness, tensile strength, folding endurance, percentage of moisture content and water vapour transmission rate. All prepared formulations indicated good physical stability. In-vitro permeation studies of formulations were performed by using diffusion cell apparatus. Formulation prepared with hydrophilic polymer containing permeation enhancer showed best in-vitro skin permeation through Wistar albino rat skin as compared to all other formulations. Formulation F9 showed highest flux among all the formulations and 1.369-fold enhancements in drug permeation. These results indicate that the formulation containing 10% of oleic acid with 10% isopropyl myristate give better penetration of heparin sodium through rat skin.
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