Abstract This study was undertaken towards enabling PET imaging of polymer‐based drug delivery. Iodinated doxorubicin conjugate (DOXIB) was characterised against un‐conjugated DOX within and outside a polymer formulation in tumour cell lines and tumour bearing animal models. The results provide the basis for developing the feasibility of [ 124 I]‐DOXIB PET to assess in vivo pharmacokinetics of drug formulation.
4526 Background: The American Cancer Society classifies Renal Cell Carcinoma (RCC) to be among the ten most common cancers. However, in spite of this need, effective biomarkers for early-stage detection of RCC are not yet available. The purpose of this study was to assess the diagnostic characteristics of a carcinoma-specific transmembrane N-glycoprotein biomarker, CA-62, for the detection of early-stage kidney cancer. Blinded serum samples from 204 patients were included in the clinical study, of which 68 had TNM-classified stages IA, IB, IIA or IIB renal cell carcinomas, while 136 were drawn from healthy volunteers. Methods: Quantitative measurement of serum CA-62 levels was performed using a chemiluminescent immunoassay ("JVS Diagnostics" LLC). Statistical analysis (MedCalc; version 19.7.4, MedCalc Software Ltd, Belgium, EU) was used to assess the diagnostic characteristics of the CA-62 biomarker for detection of RCC, including sensitivity and specificity, and test accuracy. Results: Significantly higher median concentrations of CA-62 were found in sera of RCC patients compared to those found in healthy controls as follows; stage I A, B (8,935 U/mL), stage II A (6,291 U/mL), stage II B (8,808 U/mL), and healthy controls (2,815 U/mL). It was expected that serum CA-62 levels would be elevated at these early stages of RCC (Stages I-IIB), demonstrating significant overexpression of this epithelial carcinoma marker during the initial stages of cancerogenesis. The results of the study are presented in the table. Area under the ROC curve (AUC) for RCC patients vs. healthy controls was 0.98 with a 95% CI (0.950-0.994), z-statistics (67.3), and a significance of p<0.0001. Conclusions: CA-62 demonstrated a 94.3% sensitivity for RCC at 96% specificity during the early stages of kidney cancer. Given that CA-62 is not specific for kidney cancer, it is reasonable to suggest that use of a combination of CA-62 with some other biomarkers that may lack the sensitivity of CA-62 but are often elevated in renal cell carcinoma patients, such as tumor-infiltrating lymphocytes and/or possibly some inflammation biomarkers. In particular, the combination of transmembrane glycoproteins CA-62 and CD105, combined with biomarkers such as Endothelial Vascular Growth Factor (EVGF) and/or a growth factor derived from platelets (PDGF) could be successfully used for kidney cancer screening in order to achieve both high sensitivity and specificity for RCC detection.[Table: see text]
3038 Background: A double-blind clinical study was conducted on 304 clinically verified blood serum samples, including 141 non-small cell lung cancer (NSCLC), 133 healthy volunteers and 30 patients with chronic obstructive pulmonary disease (COPD). The objectives of the study were: The assessment of various cancer markers and their possible combinations for detection of early (I-II) stages of non-small cell lung cancer (NSCLC) and evaluation of the best cancer markers panel as a pre-screening tool for NSCLC before Low-Dose CT scan. Methods: Quantitative measurement of various tumor markers for serum samples was carried out using electrochemiluminescent immunoassays Elecsys CA-125, ELECSYS CA 19-9, ELECSYS CYFRA 21-1 and ELECSYS SCC (COBAS, Roche Diagnostics GmbH, Germany, EU), enzyme immunoassay CA15-3-ELISA-BEST, CEA-ELISA-BEST, NSE-ELISA-BEST (JSC "VECTOR-BEST", RF) and immunochemiluminescent analysis CLIA-CA-62 (LLC "JVS Diagnostics", RF). The results were compared to the literature data for other biomarkers and their panels. Results: Unlike other tumor markers, which are expressed proportionally to tumor size, the marker for epithelial carcinomas CA-62 is expressed from Stage I and demonstrated the highest diagnostic results in detecting early stages (I-II) of NSCLC. The biomarkers CYFRA 21-1 and SCC do not have sufficient sensitivity and specificity to diagnose asymptomatic lung cancer. However, the addition of cytokeratin 19 CYFRA 21-1 to glycoproteins CA-62 and CEA increases the specificity by eliminating false positive results, which significantly improves the diagnostic value of the cancer marker signature (CA-62, CEA and CYFRA 21-1): 100% Specificity, 93% Sensitivity, 100% PPV, 94% NPV and 94% test accuracy. Conclusions: The results of the study demonstrated that using the biomarkers signature (CA-62, CEA and CYFRA 21-1) allows increasing the specificity of CT scan for patients with suspicious abnormalities on the tomogram, improving the interpretation of visualized localized lesion, and improving the accuracy of differential diagnosis at detecting early stages of LC up to 94%. In the prospective, adding cancer markers panel signature (CA-62, CEA and CYFRA 21-1) to the current lung cancer risk assessment system as a pre-screening tool for LDCT may improve the quality of early-stage Lung cancer detection by significant increasing the sensitivity and by reducing the proportion of false positive results. [Table: see text]
This review describes block copolymer-based systems that are used in drug formulation development. The use of amphiphilic block copolymers to modify pharmacological performance of various classes of drugs attracts more and more attention. This is largely attributable to the high tendency of block copolymer-based drug formulations to self-assemble, as well as flexibility of block copolymer chemistry, which allows precise tailoring of the carrier to virtually any chemical entity. Combination of these features allows adjustment of block copolymer-based drug formulations to achieve the most beneficial balance in drug biological interactions with the systems that control its circulation in and removal from the body and its therapeutic activity. The following major aspects are considered: 1) physical properties of formulations and the methods used to adjust these properties towards the highest pharmacological performance of the product; 2) combinatorial methods for optimisation of block copolymer-based formulations; 3) biological response modifying properties of block copolymer-based formulations.
Introduction . the ability of the small intestine (internalization) to absorb water-soluble anticancer cytostatics determines the possibility of their oral administration. the ex-vivo express method that simulates the internalization of substances using a modified technique of an isolated «inverted» segment of the rat small intestine with flash chemiluminescence is adequate to solve the problem. Objectives : to evaluate the absorption of the new water-soluble anticancer cytostatics with different properties from the rat small intestine for preclinical study by oral administration. M aterial and methods . conjugated with acridinium ( Acridinium NHS Ester, Toronto Research Chemicals, Canada) cytostatics were studied: low molecular weight (1) anthrafuran-acridinium (MW 0.8 kDa) and high molecular weight (2) aimpila-acridinium (MW 105 kDa) and (3) L-lysine-α-oxidase (LO-acridinium, MW 122 kDa). absorption was determined in a modified model of an isolated «inverted» segment of the rat small intestine using flash-chemiluminescence with the calculation of the relative light units (RLu). Results . It was shown that the absorption level of acridinium-conjugated cytostatics depending on molar concentration ranged from 55 % (1) to 1.7–11 % (2, 3) and 2500 (1) to 9.2–188 nmol/l (2, 3), respectively. the level of internalized anthrafuran-acridinium (55 %) was consistent with the known value of the effective non-conjugated cytostatic oral dose, which was two times higher than equitherapeutical parenteral dose: 100 mg/kg vs 50 mg/kg. Conclusion . the data obtained allow us to consider ex vivo express method for preclinical study of the various water-soluble anticancer cytostatics for screening and identification of an opportunity for oral administration and estimation of starting dose. the method has a good correlation with in vivo tests and economically favorable due to a quick response and small number of the tested agent.
At the present, a high potential of epigallocatechin-3-gallate (EGCG) as a new preventive and therapeutic agent in oncology and several other indications is well established. EGCG exerts its antitumor activity through induction of cell cycle arrest and apoptosis, inhibition of tumor angiogenesis, migration, and metastasisdue to its ability to interact with multiple targets in cancer cell. Unfortunately, very low oral bioavailability of EGCG prevents its efficient development as novel medicine. In this work, we have developed a polymer based nano-formulation of EGCG that significantly improved its oral bioavailability by increasing systemic exposure of the compound by about8-fold. This formulation comprises a well-known inactive ingredient non-ionic blockcopolymer Pluronic F127 that has recently been successfully used to increase bioavailability of another promising phytonutrient, 3,3`-diindolylmethane. The pharmacokinetic parameters established in the present study revealed that AUC and Cmax of the new formulation dosed at 500 mg/kg were 578.5 ± 73.8 μgâh/mL and 49.3 ± 2.9 μg/mL, while in the case of control EGCG administered in the equivalent dose AUC and Cmax were 72.9 ± 14.7 μgâh/mL, and 10.7 ± 1.1 μg/mL.
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