PURPOSE: Current therapy for lung cancer involves multimodality therapies. However, many patients are either refractory to therapy or develop drug resistance. KRAS and epidermal growth factor receptor (EGFR) mutations represent some of the most common mutations in lung cancer, and many studies have shown the importance of these mutations in both carcinogenesis and chemoresistance. Genetically engineered murine models of mutant EGFR and KRAS have been developed that more accurately recapitulate human lung cancer. Recently, using cell-based experiments, we showed that platinum-based drugs and the antidiabetic drug rosiglitazone (PPARgamma ligand) interact synergistically to reduce cancer cell and tumor growth. Here, we directly determined the efficacy of the PPARgamma/carboplatin combination in these more relevant models of drug resistant non-small cell lung cancer. EXPERIMENTAL DESIGN: Tumorigenesis was induced by activation of either mutant KRAS or EGFR. Mice then received either rosiglitazone or carboplatin monotherapy, or a combination of both drugs. Change in tumor burden, pathology, and evidence of apoptosis and cell growth were assessed. RESULTS: Tumor burden remained unchanged or increased in the mice after monotherapy with either rosiglitazone or carboplatin. In striking contrast, we observed significant tumor shrinkage in mice treated with these drugs in combination. Immunohistochemical analyses showed that this synergy was mediated via both increased apoptosis and decreased proliferation. Importantly, this synergy between carboplatin and rosiglitazone did not increase systemic toxicity. CONCLUSIONS: These data show that the PPARgamma ligand/carboplatin combination is a new therapy worthy of clinical investigation in lung cancers, including those cancers that show primary resistance to platinum therapy or acquired resistance to targeted therapy. 相似文献
Objectives: Cranberries, high in polyphenols, have been associated with a favorable glycemic response in patients with type 2 diabetes and also are beneficial for oral health. Because type 2 diabetes mellitus and periodontal disease have a physiological relationship, this study aimed to evaluate the hypothesis that cranberry juice enriched with omega-3 will improve glycemic and lipid profiles and periodontal status in patients with diabetes with periodontal disease.
Materials and Methods: In this randomized clinical trial, 41 patients with diabetes (age 35–67 years) with periodontal disease were recruited and randomly assigned to 4 groups: control (C; n = 12), receiving omega-3 (I1; n = 10, 1 g/ twice daily), cranberry juice (I2; n = 9, 200 ml, twice daily), and cranberry juice enriched with omega-3 (I3; n = 10, 200 ml, containing 1 g omega-3) twice daily for 8 weeks. Nonsurgical periodontal therapy was provided for all patients during the study. Fasting blood glucose and glycated hemoglobin, lipid profile, probing depth, anthropometric indices, and 3-day 24-hour dietary recalls were measured pre- and postintervention.
Results: Glycated hemoglobin was decreased significantly in I1 and I3 groups. Serum high-density lipoprotein cholesterol (HDL-C) levels increased significantly in the I3 group compared to baseline and compared to I1 and I2 groups. Probing depth was significantly reduced in all groups postintervention.
Conclusion: Consumption of cranberry juice enriched with omega-3 can be beneficial as adjuvant therapy with nonsurgical periodontal therapy in decreasing glycated hemoglobin, increasing HDL-C, and improving periodontal status in patients with diabetes with periodontal disease. 相似文献
A variety of bacteriocins originate from lactic acid bacteria, which have recently been modified by scientists. Many strains of lactic acid bacteria related to food groups could produce bacteriocins or antibacterial proteins highly effective against foodborne pathogens such as Staphylococcus aureus, Pseudomonas fluorescens, P. aeruginosa, Salmonella typhi, Shigella flexneri, Listeria monocytogenes, Escherichia coli O157:H7, and Clostridium botulinum. A wide range of bacteria belonging primarily to the genera Bifidobacterium and Lactobacillus have been characterized with different health‐promoting attributes. Extensive studies and in‐depth understanding of these antimicrobials mechanisms of action could enable scientists to determine their production in specific probiotic lactic acid bacteria, as they are potentially crucial for the final preservation of functional foods or for medicinal applications. In this review study, the structure, classification, mode of operation, safety, and antibacterial properties of bacteriocins as well as their effect on foodborne pathogens and antibiotic‐resistant bacteria were extensively studied. 相似文献
One of the major oral health conditions worldwide is dental caries. Light-absorption-based thermophotonic diagnostic imaging is well positioned for this challenge thanks to its speed, safety, and high molecular contrast advantages. In this work, a multispectral (MS) truncated-correlation photothermal coherence tomography (TC-PCT) imaging modality is introduced for the detection of bacterial-induced dental caries. MS TC-PCT provided thorough information about optimal lesion contrast and type of dental defects such as caries in teeth. The experimental results were validated using micro-computed tomography (µCT) including quantitative lesion depth profiles at wavelengths in the 675-700 nm range. MS TC-PCT gives rise to hard-tissue biomedical diagnostic applications such as bone and dental imaging. 相似文献
PPARgamma is a member of the nuclear receptor family for which agonist ligands have antigrowth effects. However, clinical studies using PPARgamma ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPARgamma activation with chemotherapeutic agents in current use for specific cancers. We observed a striking synergy between rosiglitazone and platinum-based drugs in several different cancers both in vitro and using transplantable and chemically induced "spontaneous" tumor models. The effect appears to be due in part to PPARgamma-mediated downregulation of metallothioneins, proteins that have been shown to be involved in resistance to platinum-based therapy. These data strongly suggest combining PPARgamma agonists and platinum-based drugs for the treatment of certain human cancers. 相似文献
BACKGROUND: Rapid and effective pain relief in acute traumatic limb injuries (ATLI) is one of the most important roles of emergency physicians. In these situations, opioid addiction is an important concern because of the dependency on opioids. The study aims to compare the effectiveness of intravenous (IV) fentanyl versus morphine in reducing pain in patients with opioid addiction who suffered from ATLI. METHODS: In this double-blind randomized clinical trial, 307 patients with ATLI, who presented to the emergency department (ED) from February 2016 to April 2016, were randomly divided into two groups. One group (152 patients) received 0.1 mg/kg IV morphine. The other group (155 patients) received 1 mcg/kg IV fentanyl. Patients’ demographic data, pain score at specific intervals, vital signs, side effects, satisfaction and the need for rescue analgesia were recorded. RESULTS: Eight patients in the morphine group and five patients in the fentanyl group were excluded. Pain score in the fentanyl group had a significant decrease at 5-minute follow-up (P value=0.00). However, at 10, 30, and 60-minute follow-ups no significant differences were observed between the two groups in terms of pain score reduction. The rescue analgesia was required in 12 (7.7%) patients in the fentanyl group and in 48 (31.6%) patients in the morphine group (P value=0.00). No significant difference was observed regarding side effects, vital signs and patients’ satisfaction between the two groups. CONCLUSION: Fentanyl might be an effective and safe drug in opioid addicts suffering from ATLI. 相似文献
Pd doped single-walled carbon nanotubes as an enhanced physical transducer with phenylalanine amino acid can be efficiently used as a biocompatible nanoreceptor to detect proteins. DFT/B3LYP was used to calculate the optimized geometries, energies and electron density parameters to determine the stability and reactivity of the nanoreceptor. Among different adsorbed configurations of phenylalanine, the amine and carboxylic acid sites have higher adsorption energies and more stable complexes. With direct strong chemical adsorption of phenylalanine amino acid onto the Pd doped single-walled carbon nanotube, the free active carboxylic acid group of the amino acid can react with free amine groups on the surface of the proteins. More over the π–π stacking interaction between the free aromatic ring of adsorbed phenylalanine amino acid onto the functionalized single-walled carbon nanotube and the aromatic rings of the proteins also contributes to the intelligent detection of proteins. Frontier molecular orbital and molecular electrostatic potential (MPE) surface studies have been employed to investigate the active sites of the nanoreceptor. The effects of different solvents on the structural and electronic properties were investigated. Finally, in order to investigate biological function of the biosensor, docking studies were performed.Early detection of proteins could help to reduce disease progress. The amino acid hybrid with the Pd/SWCNT supporting enhanced transducer provides a high sensitivity biocompatible bioelectrode in nanobiosensors for use in early disease diagnosis.相似文献