Moonlight functions of glycolytic enzymes in cancer

Since an extensive genome research has started, basic principle “one gene—one protein—one function” was significantly revised. Many proteins with more than one function were identified and characterized as “moonlighting” proteins, which activity depend not only on structural peculiarities but also on compartmentation and metabolic environment. It turned out that “housekeeping” glycolytic enzymes show important moonlight functions such as control of development, proliferation, apoptosis, migration, regulation of transcription and cell signaling. Glycolytic enzymes emerged very early in evolution and because of the limited content of genomes, they could be used as ancient regulators for intercellular and intracellular communication. The multifunctionality of the constitutively expressed enzymes began to serve cancer cell survival and growth. In the present review we discuss some moonlight functions of glycolytic enzymes that important for malignant transformation and tumor growth

Материалы для создания тканеинженерных конструкций методом 3D-биопечати при восстановлении хрящевой и мягких тканей

3D Bioprinting is a dynamically developing technology for tissue engineering and regenerative medicine. The main advantage of this technique is its ability to reproduce a given scaffold geometry and structure both in terms of the shape of the tissue-engineered construct and the distribution of its components. The key factor in bioprinting is bio ink, a cell-laden biocompatible material that mimics extracellular matrix. To meet all the requirements, the bio ink must include not only the main material, but also other components ensuring cell proliferation, differentiation and scaffold performance as a whole. The purpose of this review is to describe the most common materials applicable in bioprinting, consider their properties, prospects and limitations in cartilage restoration.3D-биопечать - динамично развивающаяся технология тканевой инженерии и регенеративной медицины. Основным преимуществом данного метода является возможность воспроизведения заданной геометрии и структуры скаффолда как в отношении формы тканеинженерной конструкции, так и распределения ее компонентов. Ключевым фактором биопечати являются биочернила - биосовместимый материал, имитирующий внеклеточный матрикс с инкорпорированными в него клетками. Для соответствия всем предъявляемым требованиям биочернила должны включать в себя не только основной компонент, но и другие составляющие, обеспечивающие пролиферацию, дифференцировку клеток и функционирование тканевой конструкции в целом. Целью обзора является анализ свойств, возможностей и ограничений в использовании наиболее распространенных материалов для биопечати скаффолдов хрящевой ткани

Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways

Sherpa Romeo blue journal. Open access article. Creative Commons Attribution 3.0 License (CC BY 3.0) applies.We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from “traditional” expression biomarkers that only assess concentrations of single genes.Ye

Оценка влияния однонуклеотидного полиморфизма val158met гена катехол-О-метилтрансферазы (СОМТ) на эффективность спинальной аналгезии в 1 сутки после лапароскопических операций по поводу колоректального рака (пилотное исследование)

The aim: To assess the effect of COMT G1947A genetic polymorphism (val158met) on the efficacy of spinal analgesia on day 1 after laparoscopic surgery for colorectal cancer.Material and methods. In a pilot study involving 100 patients with colorectal cancer, operated through laparoscopic access, using spinal analgesia (10.0–12.5 mg of bupivacaine + 200 mcg of morphine), the frequency of COMT gene G1947A (val158met) polymorphism, the intensity of pain on day 1 after surgery, the frequency and severity of nausea, vomiting, skin itching, the need for additional analgesia have been assessed.Results. The frequency distribution of alleles val/val (25%), val/met (45%) and met/met (30%) was consisted with Hardy-Weinberg equilibrium (χ2=0.96; P>0.05) and was not significantly different from the healthy donor group. In the groups of patients with various COMT alleles of val158met polymorphism, the studied parameters also did not differ significantly.Conclusion. Study did not find significant link between spinal analgesia efficacy on day 1 after laparoscopic surgery for colorectal cancer and COMT rs4680 G1947A (val158met) polymorphism. Further research to enhance the power of the study is warranted to reach the final conclusions.Цель: оценка влияния SNP val158met гена COMT на эффективность спинальной аналгезии в 1 сутки после лапароскопических операций по поводу колоректального рака.Материал и методы. В пилотном исследовании, включавшем 100 пациентов c колоректальным раком, оперированных лапароскопическим доступом, с использованием в комплексе анестезиологического пособия спинальной аналгезии (10–12,5 мг бупивакаина + 200 мкг морфина), оценили частоту полиморфизма val158met гена COMT, интенсивность боли в 1 сутки после операции, частоту и выраженность тошноты, рвоты, кожного зуда, потребность в дополнительном обезболивании.Результаты. Распределение частот аллелей val/val (25%), val/met (45%) и met/met (30%) подчинялось закону Харди-Вайнберга (χ2=0,96; р>0,05) и статистически значимо не отличалось от группы здоровых доноров. В группах носителей различных аллелей SNP val158met исследуемые показатели статистически значимо не отличались.Заключение. Зависимости эффективности спинальной аналгезии в 1 сутки после лапароскопических операций по поводу колоректального рака от SNP val158met гена СОМТ не выявили. Для получения окончательных выводов необходимо проведение дальнейших исследований

Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate’s role in the malignant transformation becomes more relevant in the light of the “atavistic theory of carcinogenesis,” which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect

Moonlight functions of glycolytic enzymes in cancer

Since an extensive genome research has started, basic principle “one gene—one protein—one function” was significantly revised. Many proteins with more than one function were identified and characterized as “moonlighting” proteins, which activity depend not only on structural peculiarities but also on compartmentation and metabolic environment. It turned out that “housekeeping” glycolytic enzymes show important moonlight functions such as control of development, proliferation, apoptosis, migration, regulation of transcription and cell signaling. Glycolytic enzymes emerged very early in evolution and because of the limited content of genomes, they could be used as ancient regulators for intercellular and intracellular communication. The multifunctionality of the constitutively expressed enzymes began to serve cancer cell survival and growth. In the present review we discuss some moonlight functions of glycolytic enzymes that important for malignant transformation and tumor growth

Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate’s role in the malignant transformation becomes more relevant in the light of the “atavistic theory of carcinogenesis,” which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect

COMT val158met Polymorphism and Spinal Analgesia Efficacy of Laparoscopic Surgery for Colorectal Cancer (a Pilot Study)

The aim: To assess the effect of COMT G1947A genetic polymorphism (val158met) on the efficacy of spinal analgesia on day 1 after laparoscopic surgery for colorectal cancer.Material and methods. In a pilot study involving 100 patients with colorectal cancer, operated through laparoscopic access, using spinal analgesia (10.0–12.5 mg of bupivacaine + 200 mcg of morphine), the frequency of COMT gene G1947A (val158met) polymorphism, the intensity of pain on day 1 after surgery, the frequency and severity of nausea, vomiting, skin itching, the need for additional analgesia have been assessed.Results. The frequency distribution of alleles val/val (25%), val/met (45%) and met/met (30%) was consisted with Hardy-Weinberg equilibrium (χ2=0.96; P>0.05) and was not significantly different from the healthy donor group. In the groups of patients with various COMT alleles of val158met polymorphism, the studied parameters also did not differ significantly.Conclusion. Study did not find significant link between spinal analgesia efficacy on day 1 after laparoscopic surgery for colorectal cancer and COMT rs4680 G1947A (val158met) polymorphism. Further research to enhance the power of the study is warranted to reach the final conclusions

On the Pathomorphological Pattern of the Efficiency of Photodynamic Therapy of Murine Melanoma B16 Using a New Photosensitizer Based on Chlorin e6 Conjugate with a Prostate-Specific Membrane Antigen

Photodynamic therapy (PDT) is an effective treatment for a number of solid malignancies. In this work, the antitumor efficacy of photodynamic therapy for murine B16 melanoma with intravenous administration of a new photosensitizer (PS) based on the chlorin e6 conjugate with a prostate-specific membrane antigen (PSMA) was studied in vivo. We have previously published the data obtained in the first part of the study: the dynamics of PS accumulation in the tumor and surrounding tissues and the antitumor efficacy of the photodynamic therapy, which was evaluated by the regression parameters and morphological characteristics of the tumors—including by the complete regression of the tumors, the absolute growth rate of the tumors among the mice with continued tumor growth, and an increase in life expectancy compared to the control. The criterion for a complete cure was the absence of signs of tumor recurrence within 90 days after therapy. The conducted studies demonstrated the high efficiency of the new photosensitizer for the photodynamic therapy of B16 melanoma. This article presents a continuation of this work, including histological studies of the zones exposed to laser irradiation on the 21st day after treatment and an assessment of the therapeutic potential of photodynamic therapy for the destruction of tumor cells. Pathological studies in the zones of photodynamic exposure revealed that the effectiveness of the PDT depended on the PS dose and the laser irradiation parameters