The pathological state of a human body leads to altered biochemical composition of body fluids. Conventional biochemical analysis of body fluids is notable for its low‐informative value in localizing a particular pathology. As an alternative, Raman spectroscopy provides detailed evaluation of blood characteristics at the molecular level. Raman blood spectra are characterized by multicollinearity as well as by the presence of autofluorescence background and noises of different nature. Choice of a proper method for experimental data processing of blood spectra is crucial for obtaining statistically reliable information regarding a pathological process in the body. This study examines different approaches to multidimensional analysis of the various‐size Raman spectral dataset of human blood samples by a cost‐effective Raman setup in a clinical setting. To discriminate blood samples by the pathology type, statistical processing of experimental data is performed by factor analysis, logistic regression, discriminant analysis, classification tree, projection to latent structures discriminant analysis (PLS‐DA), and soft independent modeling of class analogies. Comparative analysis of the discussed multivariate methods demonstrates that the PLS‐DA method (sensitivity 0.75, specificity 0.81, and accuracy 0.76) proved to be the most effective for the classification of blood samples by cancer localization. In terms of classification for the presence of hyperproteinemia, the most efficient are the logistic regression method (sensitivity 0.89, specificity 0.99, and accuracy 0.97) and the discriminant analysis method (sensitivity 0.83, specificity 1.0, and accuracy 0.97). In general, the selected multivariate methods could serve as a reliable tool for analyzing spectral characteristics of body fluids.
Introduction: The creation of highly effective original anticancer drugs remains an urgent direction of scientific research in tumor therapy. One of the promising groups in this regard is indolocarbazoles and their derivatives, which are capable of initiating various pathways of tumor cell death. The aim of the study was to evaluate an antiproliferative activity of a new, Russian derivative of N-glycoside substituted indolocarbazole 6-amino-12-(α-L-arabinopyranosyl)indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione (LCS-1208) on models of transplantable tumors of mice and on human tumors in Balb/c nude mice.
Materials and methods: Indolocarbazole sensitivity to LCS-1208 was assessed on transplantable tumors of mice – lymphatic leukemia L-1210, cervical carcinoma (CC-5), and colon adenocarcinoma (CAC) by five-fold intraperitoneal administration (ip) of the LCS-1208 substance in single doses of 50, 75, 100 mg/kg. Investigation into the effectiveness of the LCS-1208 lyo dosage form was performed on subcutaneous xenografts of human colon cancer SW620 by an intravenous administration (iv). The antitumor effect was evaluated by the tumor growth inhibition (TGI) and an increase in life span (ILS) of the treated animals as compared with the control ones. Evaluation of specific antitumor activity on xenografts was performed according to the tumor/control (T/C%) criterion (maximum criterion T/C≤42%).
Results and discussion: According to the results of the study, the most sensitive to the action of the LCS-1208 substance in the case of an ip administration of a total dose of 375 mg/kg were CAC with TGI=97–62%, p≤0.001 up to 16 days after the treatment, and ILS=36% (criteria for TGI≥70% and ILS≥25%). On xenografts of a human colon cancer SW620, the effectiveness of the LCS-1208 lyo drug dosage form within the range of total doses from 50 to 150 mg/kg in case of iv to Balb/c nude mice was set at T/C = 35–2% (criterion T/C<42%).
Conclusion: The presented results suggest possible effectiveness of LCS-1208 in treatment of colon malignant tumors of humans.
The aim of this study was to explore the mechanisms of action of alsevirone in prostate cancer (PC) in vitro and in vivo: CYP17A1 inhibition, cytotoxic, apoptotic, and antitumor effects in comparison with abiraterone. The CYP17A1-inhibitory activity was investigated in rat testicular microsomes using high-performance liquid chromatography. Testosterone levels were evaluated using enzyme-linked immunoassay. IC 50 values were calculated for PC3, DU-145, LNCaP, and 22Rv1 cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test. The antitumor effect in vivo was studied in DU-145 and 22Rv1 subcutaneous xenografts in Balb/c nude mice. Alsevirone reduced the CYP17A1-inhibitory activity by 98% ± 0.2%. A statistically significant reduction in the testosterone concentration in murine blood was recorded after the 7th administration of 300 mg/kg alsevirone at 0.31 ± 0.03 ng/ ml (p < .001) versus 0.98 ± 0.22 ng/ml (p = .392) after abiraterone administration and 1.52 ± 0.49 ng/ml in control animals. Alsevirone was more cytotoxic than abiraterone
национальный исследовательский университет имени академика С.П. Королева», Самара В статье представлены современные подходы к диагностике пролиферативной и непролиферативной диабетической ретинопатии. На основе патогенеза выделены изменения в генах, которые могут лежать в основе наследственной предрасположенности к данному заболеванию. В настоящее время принято считать, что патогенез диабета является многофакторным, но генетические факторы риска играют в нем фундаментальную роль. Недавние исследования в области генома выявили несколько генетических локусов, участвующих в патогенезе диабета 1-го типа и 2-го типа. Установлено, что механизмы патогенеза диабетической ретинопатии разнообразны и достаточно сложны, однако немаловажную роль в них играют генетические факторы, которые, вероятно, определяют восприимчивость пациента к этой болезни, а также различия в частоте возникновения диабетической ретинопатии между индивидуумами с диабетом 1-го и 2-го типа. В ходе нашего исследования установлено, что полиморфные локусы генов VEGF rs2010963, AKR1B1 rs759853, ITGA2 rs2910964, ADRB3 rs4994, APOE rs7412, APOE 429358, рассматриваемые независимо друг от друга, не связаны с развитием диабетической ретинопатии в изученной группе больных сахарным диабетом 2-го типа. На наш взгляд, отрицательный результат данного исследования обусловлен гетерогенностью изученной группы по возрасту и стажу сахарного диабета, а также его различной компенсацией. Эти известные факторы риска диабетической ретинопатии могли помешать выявлению более слабых наследственных предрасположенностей.
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