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Background

The assessment of epidermal growth factor receptor (EGFR) mutations is crucial for the management of patients with lung adenocarcinoma. Circulating tumor DNA (ctDNA)-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity.

Patients and Methods

Consecutive patients diagnosed with EGFR-mutant lung adenocarcinoma in tumor biopsy were included in this study. Plasma samples were obtained at different time points during the course of the disease. EGFR mutations in plasma were quantified using BEAMing (beads, emulsions, amplification, and magnetics) or digital PCR and were correlated with mutations in tumor and with radiologic response and progression.

Results

Two hundred twenty-one plasma samples from 33 patients were analyzed. EGFR mutations in plasma were detected in 83% of all patients and 100% of those with extrathoracic metastases. The dynamics of the EGFR mutation load predicted response in 93% and progression in 89% of cases well in advance of radiologic evaluation. Progression-free survival for patients in whom ctDNA was not detected in plasma during treatment was significantly longer than for those in whom ctDNA remained detectable (295 vs. 55 days; hazard ratio, 17.1; P < .001).

Conclusion

The detection of EGFR mutations in ctDNA showed good correlation with that in tumor biopsy and predicted tumor response and progression in most patients. The liquid biopsy for ctDNA-based assessment of EGFR mutations is a reliable technique for diagnosis and follow-up in patients with EGFR-mutant lung adenocarcinoma in routine clinical practice.  相似文献   
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Introduction: Cancer is a leading cause of death worldwide and efficient new strategies are urgently needed to combat its high mortality and morbidity statistics. Fortunately, over the years, nanotechnology has evolved as a frontrunner in the areas of imaging, diagnostics and therapy, giving the possibility of monitoring, evaluating and individualizing cancer treatments in real-time.

Areas covered: Polymer-based nanocarriers have been extensively studied to maximize cancer treatment efficacy and minimize the adverse effects of standard therapeutics. Regarding diagnosis, nanomaterials like quantum dots, iron oxide nanoparticles or gold nanoparticles have been developed to provide rapid, sensitive detection of cancer and, therefore, facilitate early treatment and monitoring of the disease. Therefore, multifunctional nanosystems with both imaging and therapy functionalities bring us a step closer to delivering precision/personalized medicine in the cancer setting.

Expert opinion: There are multiple barriers for these new nanosystems to enter the clinic, but it is expected that in the near future, nanocarriers, together with new ‘targeted drugs’, could replace our current treatments and cancer could become a nonfatal disease with good recovery rates. Joint efforts between scientists, clinicians, the pharmaceutical industry and legislative bodies are needed to bring to fruition the application of nanosystems in the clinical management of cancer.  相似文献   

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Vaccine developers are required to submit a clinical trial application to the authorities in each country where a clinical trial will be conducted. The application has to be made both to the relevant Ethics Committees and to the National Regulatory Authorities, and only after appropriate clearance by both can a clinical trial commence.  相似文献   
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IntroductionSexual life of psychiatric patients, including risk behaviors related to sexually transmitted diseases, remains a poorly studied area, especially in those with severe mental illnesses.AimsTo assess some aspects of lifetime sexual behavior of psychiatric inpatients.MethodsPatients consecutively admitted to a psychiatric unit in a general hospital were interviewed about partner-related lifetime sexual behavior.Main Outcome MeasuresA semi-structured interview developed by the authors was used to collect information concerning their general sexual experience throughout life, homosexual and heterosexual relations, and relations with partners who were intravenous drug users (IVDU), HIV carriers or suffering from AIDS, and with sex workers. In each of these areas, time elapsed since last sexual contact; number of partners in previous year, frequency of these relations and condom use were investigated.ResultsFive hundred forty-six patients (306 men and 240 women) were assessed, and 87.7% of them reported sexual relations at some point during their life. Of these, 90% reported heterosexual and 10% homosexual or bisexual sexual contacts. Further, 11.06% had had at least one partner who was an IVDU; 8.1% an HIV-positive partner, and 32.4% (50% of the men) had paid for sex. Overall 49.79% of the total sample reported never using condoms in their sexual relations, with similar percentages for those with HIV-positive (46%) and IVDU (47%) partners. Of those who paid for sex, 29% never used condoms.ConclusionsPsychiatric patients admitted to a general hospital psychiatric unit have sexual experience close to the general population, with a higher percentage of homosexual contacts and lower rates of condom use, even in higher risk situations, such as men having sex with men, and partners who are HIV-positive or IVDUs. This information obliges clinicians to systematically explore the sexual behavior of psychiatric patients, evaluate risk behaviors, and adopt measures to promote safe sex practices in this population. Gonzalez-Torres MA, Salazar MA, Inchausti L, Ibañez B, Pastor J, Gonzalez G, Carvajal MJ, Fernandez-Rivas A, Madrazo A, Ruiz E, and Basterreche E. Lifetime sexual behavior of psychiatric inpatients.  相似文献   
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Gentamicin (GEN) is an aminoglycoside antibiotic with a potent antibacterial activity against a wide variety of bacteria. However, its poor cellular penetration limits its use in the treatment of infections caused by intracellular pathogens. One potential strategy to overcome this problem is the use of particulate carriers that can target the intracellular sites of infection. In this study GEN was ion-paired with the anionic AOT surfactant to obtain a hydrophobic complex (GEN-AOT) that was formulated as a particulated material either by the precipitation with a compressed antisolvent (PCA) method or by encapsulation into poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The micronization of GEN-AOT by PCA yielded a particulated material with a higher surface area than the non-precipitated complex, while PLGA NPs within a size range of 250-330 nm and a sustained release of the drug over 70 days were obtained by preparing the NPs using the emulsion solvent evaporation method. For the first time, GEN encapsulation efficiency values of ~100% were achieved for the different NP formulations with no signs of interaction between the drug and the polymer. Finally, in vitro studies against the intracellular bacteria Brucella melitensis, used as a model of intracellular pathogen, demonstrated that the bactericidal activity of GEN was unmodified after ion-pairing, precipitation or encapsulation into NPs. These results encourage their use for treatment for infections caused by GEN-sensitive intracellular bacteria.  相似文献   
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Identification of glycans in amphibian testis has shown the existence of N‐acetylgalactosamine (GalNAc)‐containing carbohydrates. Labeling of the sperm acrosome with GalNAc‐binding lectins has allowed the identification of GalNAc‐containing glycans in this organelle. Futhermore, this specific labeling of the acrosome has allowed the study of acrosomal biogenesis by lectin histochemistry. However, the testis of Xenopus laevis has never been analyzed by lectin histochemistry to locate GalNAc‐containing glycoconjugates. The aim of this work was to elucidate the expression of GalNAc in glycoconjugates of Xenopus testis using five specific lectins. The results showed that most of the lectins labeled the interstitium with variable intensity. However, labeling of the different spermatogenetic germ cell types showed different labeling patterns. Some lectins produced weak or very weak staining in germ cells, for example, horse gram Dolichos biflorus agglutinin, which labeled most of the germ cell types, and lima bean Phaseolus lunatus agglutinin, which weakly labeled only spermatogonia, but did not stain other germ cells. By contrast, Maclura pomifera lectin (MPL) moderately labeled all germ cell types, except mature sperm. Labeling with other lectins was seen only at later stages, suggesting variations involved in the spermatogenetic development. Thus, snail Helix pomatia agglutinin labeled spermatids, but neither spermatogonia nor spermatocytes, while soybean Glycine max agglutinin (SBA) labeled from preleptotene spermatocytes to later stages. The periphery of the acrosome was labeled with MPL and SBA, but no specific labeling of the acrosomal content was seen with any lectin. Thus, the GalNAc‐binding lectins that have been used as acrosomal markers in some amphibians cannot be used in Xenopus testis, suggesting that acrosomal glycoconjugates in amphibians are species specific. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.  相似文献   
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Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and hematologic tumors. Novel drugs targeting this tyrosine kinase receptor are under development, and early clinical trials are showing promising activity in non-small cell lung cancer patients with ALK+ tumors. Here, we review the structure and function of the ALK receptor, the mechanisms associated with its deregulation in cancer, methods for ALK detection in tumor samples, its potential as a new marker for candidate patient selection for tailored therapy, and novel drugs under development that target ALK.  相似文献   
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