Энергетический обмен стволовых клеток глиомы

Institute of Neurology and NeurosurgeryTumor cell energy metabolism is often invoked as marker of aggressiveness and resistance in the study of cancer. Warburg was the first researcher to propose the high consumption of glucose and reduction of tumor cell oxidative metabolism as prominent feature of cancer cells. In clinical practice, this feature is used in PET imaging (positron emission tomography) to visualize the 2-FDG antimetabolite enhancing lesions. In reality, not all tumors are characterized by high levels of glycolysis. To highlight certain features affected by glucose and energy, four types of cancer stem cells (CSCs) were isolated from the third degree of malignancy gliomas (anaplastic glioma, WHO, World Health Organization). The NADH cells’ levels of CSCs in sphere cultures where evaluated and compared to a proliferation index. Surprisingly, the cells with the highest proliferation index showed a lowest ratio of NADH/ proliferation. Thus, the energy status of cancer stem cells lines derived from gliomas is inversely correlated to proliferation in vitro. Glucose dependency varied considerably among the four types of glioma stem cells. In one case, NADH levels were maintained in the absence of glucose by substitution with glutamine. DCA (dichloroacetat) is an energy modulator acting as a mitochondrial function stimulator. In our experiments, DCA could stimulate NADH production, showing the possibility of mitochondrial function recovery in glioma cancer stem cells. В исследовании агрессивности и сопротивления рака часто используются особенности энергетического метаболизма опухолевых клеток. Варбург был первым, кто поставил акцент на высокий уровень потребления глюкозы и снижения окислительной функции опухолевых клеток. В клинической практике эта функция используется в ПЭТ (позитронно-эмиссионной томографии), сканирование с помощью метаболит 2-FDG. На самом деле, не все опухоли можно охарактеризовать высоким уровнем гликолиза. Для характеристики зависимости от глюкозы и выделения некоторых энергетических особенностей были выделены из глиомы четыре типа стволовых клеток, с сопоставимой степени злокачественности (3 anaplastic – 3 анапластической, Всемирная Организация Здравоохранения). Удивительно, что стволовые клетки с высоким индексом пролиферации показали самый низкий уровень NADH (энергетический эквивалент снижения). Энергетический статус нормальных нервных стволовых клеток, вызванный NADH, был самым высоким. Зависимость от глюкозы значительно различалась между четырьмя типами стволовых клеток глиомы, а в одном случае, уровень NADH был сохранен в отсутствие глюкозы при замещении глутамина. При лечении с DCA (dichloroacetat) производства NADH можно стимулировать, показывая вожможность частичного восстановления митохондриальной функции опухоли

Glucose metabolism in cancer and the role of ketogenic diet

Department of Biochemistry and Clinical Biochemistry, Nicolae Testemitsanu State University of Medicine and Pharmacy, Chisinau, the Republic of MoldovaBackground: One of the fundamental metabolic characteristics of cancer tissues is high consumption of glucose by cancer cells. The purpose of this article is determination of the features in the energy metabolism of cancer cells, elucidation of energy metabolism due to the major nutritive substrates, such as glucose and glutamine, evaluation of lactate dehydrogenase (LDH) as a potential marker of malignancies, estimation of the ketogenic diet in the treatment of cancer. The cells with higher degree of proliferation have a lower level of reduced Nicotinamide Adenine Dinucleotide (NADH), confirming the hypothesis: anabolic processes are predominant in cancer. The preferred way of glucose utilization in cancer tissues is the conversion of pyruvate to lactate, a phenomenon known as aerobic glycolysis or Warburg effect. Tumors with a high level of aerobic glycolysis are the most aggressive. The fact that LDHA (which catalyzes the reversible reaction of pyruvate to lactate) reflects the aggressiveness of the tumor and demonstrates the importance of aerobic glycolytic metabolism (the Warburg effect) in the survival of tumor cells. Conclusions: Multiple studies have mentioned the possibility of using glutamine instead of glucose by the cancer cells. Use of glutamine is another way of generating energy contributing to tumor cell survival. It was established that on substitution of glucose with ketone bodies (ketogenic diet), cancer cells can not adapt and die. Modulation of energy metabolism represents a new stage in the treatment of cancer. The substitution of glucose with lipids in the feed ration (ketogenic diet) is a non-toxic method of cancer management, both in prevention and treatment

Периоперационная эволюция фенотипа хронической сердечной недостаточности у кардиохи- рургических больных.

Background. Heart failure (HF) is a well-defined risk factor for early mortality and morbidity after cardiac surgery.We aimed to analyze the evolution of the clinical phenotype of HF at an early stage after heart surgery.Methods. The study included 126 consecutive patients with established chronic HF who fulfilled the cardiac rehabilitation program after undergoing heart surgery (62.23±8.59 years, 67.5% - men). Subjects were divided into 3 groups according to the clinical phenotype of HF: group 1 - HF with reduced left ventricular (LV) ejection fraction (EF) (HFrEF), group 2 - HF with mildly reduced LV EF (HFmrEF) and group 3 - HF with preserved LV EF (HFpEF). All patients were investigated by electrocardiography, transthoracic echocardiography, 6 minutes walk test and assessment of serum NT-proBNP level. Results. Preoperatively, 23.9% of patients had HFrEF, 24.8% - HFmrEF and 51.3% - HFpEF. Analyzing the evolution of the HF phenotype in the early postoperative period, we found that most patients remained in the same group. However, among patients with preoperative HFmrEF, in 22.2% of patients there was an increase in LV EF over 50% and in 22.2% of patients was determined a reduced LV EF, p<0.001. The most obvious positive dynamic of the HF phenotype was attested in patients with HFrEF, where 37% of them presented a mildly reduced LV EF postoperatively, p <0.001. 78.9% of individuals with HFpEF remained in the same group, but 21% showed a decrease in LV EF, p<0.001. Conclusions. At the early stage after cardiac surgery, the most positive evolution of HF phenotype was noticed in the group of patients with HFrEF. Of the 44.4% of patients with HFmrEF who switched to another HF phenotype, only a half reported an increase in LV EF over 50%. The vast majority of patients with HFpEF had the same HF phenotype postoperatively.Introducere. Insuficiența cardiacă (IC) este un factor de risc bine determinat pentru mortalitate și morbiditate în perioada precoce după intervenție chirurgicală cardiacă. Ne-am propus să analizăm evoluția fenotipului clinic al IC la etapa precoce după suportarea unei operații pe cord. Materiale și metode. Studiul a inclus 126 pacienți consecutivi cu IC cronică stabilită, care au urmat programul de reabilitare cardiacă după suportarea unei intervenții chirurgicale pe cord (62,23±8,59 ani, 67,5% bărbați). Subiecții au fost divizați în 3 grupuri în funcție de fenotipul clinic de IC: grupul 1 - IC cu fracția de ejecție (FE) a ventriculului stâng (VS) redusă (IC-FErVS), grupul 2 - IC cu FE VS ușor redusă (IC-FEurVS) și grupul 3 - IC cu FE VS prezervată (IC-FEpVS). Toți pacienții au fost investigați complex prin electrocardiografie, ecocardiografie transtoracică, test de mers plat 6 minute și evaluarea nivelului seric al NT-proBNP. Rezultate. Preoperator, 23,9% de pacienți au avut IC-FErVS, 24,8% - IC-FEurVS și 51,3% - IC-FEpVS. Analizând evoluția fenotipului de IC în perioada postoperatorie precoce, s-a observat că majoritatea pacienților au rămas în cadrul aceluiași grup. Totuși, dintre pacienții cu IC-FEurVS preoperator, la 22,2% bolnavi s-a atestat IC-FEpVS la etapa postoperatorie precoce, iar la 22,2% dintre bolnavi s-a determinat IC-FErVS, p<0,001. Cea mai evidentă dinamică pozitivă a fenotipului de IC s-a atestat la pacienții cu IC-FErVS, unde 37% dintre aceștia au prezentat postoperator o FE VS ușor redusă, p<0,001. 78,9% dintre indivizii cu IC-FEpVS au rămas în același grup, iar 21% au manifestat o diminuare a fracției de ejecție a VS, p<0,001. Concluzii. În grupul de pacienți cu IC-FErVS s-a remarcat o dinamică pozitivă mai importantă a fenotipului IC la etapa precoce după intervenția chirurgicală cardiacă. Dintre cei 44,4% de pacienții cu IC-FEurVS care au manifestat tranziția spre un alt fenotip de IC, doar jumătate a atestat majorarea FE VS peste 50%. La majoritatea covârșitoare a pacienților cu IC-FEpVS s-a stabilit același fenotip al IC postoperator.Вступление. Сердечная недостаточность (СН) является установленным фактором риска смертности и заболеваемости в раннем периоде после кардиохирургического вмешательства. Целью исследования было проанализировать эволюцию клинического фенотипа СН на ранней стадии после операции на сердце. Методы. В исследовании были включены 126 последовательных пациентов с признаками и симптомами хронической СН, госпитализированных для кардиологической реабилитации после операции на сердце (62,23±8,59 года, 67,5% - мужского пола). Пациенты были разделены на 3 группы в соответствии с клиническим фенотипом СН: 1 группа - СН со сниженной фракцией выброса (ФВ) левого желудочка (ЛЖ) (СНснФВ), 2 группа - СН с промежуточной ФВ ЛЖ (СНпФВ) и 3 группа - СН с сохраненной ФВ ЛЖ (СНсохрФВ). Все пациенты были обследованы с помощью электрокардиографии, трансторакальной эхокардиографии, теста 6-минутной ходьбы и определения уровня мозгового натрийуретического пептида. Результаты. До операции, 23,9% пациентов имели СНснФВ, 24,8% - СНпФВ и 51,3% - СНсохрФВ. Анализируя эволюцию фенотипа СН в раннем послеоперационном периоде, можно отметить, что большинство пациентов остались в той же группе. Однако среди пациентов с СНпФВ в предоперационном периоде, у 22,2% больных отмечалось увеличение ФВ ЛЖ выше 50% на раннем послеоперационном этапе, а у 22,2% пациентов определялась сниженная ФВ ЛЖ, p<0,001. Наиболее очевидная положительная динамика фенотипа СН отмечена у пациентов с СНснФВ, так как у 37% из них после операции ФВ ЛЖ стала выше 40%, p<0,001. 78,9% больных с СНсохрФВ осталось в той же группе, но 21% показали снижение ФВ ЛЖ, p<0,001. Выводы. В группе пациентов с СНснФВ отмечена наиболее очевидная положительная динамика фенотипа СН на раннем этапе после кардиохирургического вмешательства. Из 44,4% пациентов с СНпФВ у которых отмечен переход к другому фенотипу СН, только у половины больных ФВ ЛЖ превысила уровень 50%. Среди пациентов с СНсохрФВ перед операцией на сердце ФВ ЛЖ сохранялась выше 50% в подавляющем большинстве случаев и после кардиохирургического вмешательства

Metastases from renal cell carcinoma presenting as gastrointestinal bleeding: two case reports and a review of the literature

BACKGROUND: Bleeding from small bowel neoplasms account for 1–4% of cases of upper gastrointestinal haemorrhage. Renal cell carcinoma constitutes 3% of all adult malignancies and often presents insidiously. Consequently 25–30% of patients have metastases at the time of diagnosis. Gastrointestinal bleeding from renal cell carcinoma metastases is an uncommon and under-recognised manifestation of this disease. CASE REPORT: In this report we describe two cases of gastrointestinal bleeding from renal cell carcinoma metastases – in one patient bleeding heralded the primary manifestation of disease and in the other signified recurrence of disease following nephrectomy. CONCLUSION: These cases highlight the importance endoscopic vigilance in cases of undiagnosed upper gastrointestinal haemorrhage, especially in patients with a past history of renal cell carcinoma

The effect of surgical ventricular restoration technics on left ventricular remodeling in different heart failure phenotypes

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiac remodeling represents a major cause of heart failure (HF) as well as cardiac morbidity and mortality [1], surgical ventricular restoration (SVR) improve left ventricular function, clinical condition and heart failure [2]. Objectives We assessed the early outcomes after open-heart surgery, which included techniques of ventricular restorations on left ventricular dimensions and function. Additionally we evaluated the effect of SVR according to the heart failure phenotypes. Material and Methods A 4 months prospective observational study enrolled 100 patients that underwent procedures of surgical ventricular restoration through Dor and Jatene method. All patients were evaluated through chest echocardiography at presentation, before surgery and at the end of heart rehabilitation program. In addition, we analyzed the left ventricle indices according to three heart failure phenotypes: group 1 (Gr.1) – HF with preserved EF, group 2 (Gr. 2) – HF with mildly reduced EF, group 3 (Gr. 3) – HF with reduced EF. Results The left ventricle diameter and volume in systole and diastole registered statistically significant differences (p &amp;lt;0.001) both in the general group and in the different clinical phenotypes of HF. The end-systolic diameter of the left ventricle decreased significantly in the general group compared to the rehabilitation stage and the preoperative by – 2, 0 ± 0, 6. Regarding the end-systolic volume of the left ventricle, the statistical significant differences (p&amp;lt;0.001, Fig.1) were marked at the stage of cardiac rehabilitation compared to the preoperative stage both in the general group with -13.0 ± 4.6. The same comparative analysis showed the relation between the groups Gr. 1: -1.2 ± 3.4, Gr. 2: -6.9 ± 8.5, Gr. 3: -42.5 ± 11.8. The systolic function of the left ventricle expressed through the EF (Fig.2) also meets a growth / improvement dynamics (p &amp;lt;0.001) assessed by comparative analysis of data at the stage of cardiac rehabilitation compared to the preoperative stage. It was found for the general group an increase of 1.0 ± 0.7, and a more obvious increase for Gr. 2: 3.6 ± 1.5 and Gr. 3: 4.2 ± 1.4. Conclusion The dynamics of left ventricular remodeling parameters in patients undergoing surgery shows statistically significant growth both in the general group and in the sub-group analysis. It induces significant decrease in the end-systolic and end-diastolic diameters and volumes of the left ventricle at the post-rehabilitation stage in all three groups. Therefore, surgical ventricular restorations influence the further positive outcomes on left ventricular function. The contraction function of the left ventricular myocardium registered a slightly positive dynamics, fact highlighted by the comparative analysis of the post-rehabilitation phase with the preoperative one, the increase of the EF being subtle in the general group and more expressed for the group with the slightly reduced ejection and with low ejection fraction. </jats:sec

The effectiveness of structured telephone support in the late phase of rehabilitation at home in patients with myocardial revascularization

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Institute of Cardiology Background Nowadays remote monitoring seems to be a promising solution for the surveillance of patients with chronic heart disease. Purpose Assessing the impact of structured telephone support in the late phase of home rehabilitation in patients with myocardial revascularization. Methods The study included 180 patients (mean age- 63.0±0.4 years, 75.6% were men, mean follow up duration- 28.8±0.5 months), discharged after completing the cardiac rehabilitation program after myocardial revascularization by coronary artery bypass grafting (81.7%) or percutaneous coronary angioplasty (18.3%). All subjects were divided into 2 groups. STS-Gr included 84 patients (mean age- 63.2±0.7 years, 69.8%- men, mean follow up- 30.5±1.1 months). In this group remote monitoring was applied through Structured Telephone Support - patients being contacted by telephone regularly with the issuance of recommendations for the correction of treatment and risk factors. Non-STS-Gr included 96 patients (mean age- 62.8±0.5 years, 78% being men, mean follow up- 28.1±0.6 months), who were not remotely monitored. At the discharge from the hospital and at the end of the surveillance, all patients underwent echocardiographycal examination, assessement of NT-proBNP level and evaluation of quality of life by SF-36 questionnaire. Results The two groups of patients were comparable in terms of NYHA functional class of heart failure, cardiovascular and non-cardiovascular comorbidities, type of myocardial revascularization. At the follow up visit, in the general group was observed a significant increase in left ventricular ejection fraction by 4.3% (p&amp;lt;0.05) and a decrease in NT-proBNP level (-935.9±357.7, p&amp;lt;0.05), with similar dynamics in both groups. The rate of cardiovascular (CV) hospitalization in the general group during surveillance was 51.2%. In STS-Gr the CV-hospitalization rate was significantly lower compared to non-STS-Gr (47% vs 61.2%, p &amp;lt;0.01). The mortality rate in the general group was 7.8% and did not differ between STS-Gr and non-STS-Gr (7.5% vs 7.9%). The quality of life of patients in the general group attested a statistically important increase of the physical composite score compared to the initial data (+32.3, p&amp;lt;0.001). The physical composite score did not show significant differences between groups at the end of the study (STS-Gr-188.2±10.2, non-STS-Gr- 194.7±7.3). At the initial stage, the mental composite score was significantly lower in STS-Gr (198.6±14.8 vs 239.6±10.6, p&amp;lt;0.05). In contrast, at the end of surveillance, the mean value of the mental composite score in STS-Gr was higher than in non-STS-Gr (246.4±7.9 vs 224.9±5.7, respectively, p&amp;lt;0.05). Conclusions Structured telephone support has been shown to be effective in reducing the rate of cardiovascular hospitalization and improving the SF-36 mental composite score of patients in the late phase of home rehabilitation after myocardial revascularization, but has not influenced mortality. </jats:sec

Perioperative evolution of chronic heart failure phenotype in patients with cardiac surgery

Background. Heart failure (HF) is a well-defined risk factor for early mortality and morbidity after cardiac surgery.We aimed to analyze the evolution of the clinical phenotype of HF at an early stage after heart surgery.Methods. The study included 126 consecutive patients with established chronic HF who fulfilled the cardiac rehabilitation program after undergoing heart surgery (62.23±8.59 years, 67.5% - men). Subjects were divided into 3 groups according to the clinical phenotype of HF: group 1 - HF with reduced left ventricular (LV) ejection fraction (EF) (HFrEF), group 2 - HF with mildly reduced LV EF (HFmrEF) and group 3 - HF with preserved LV EF (HFpEF). All patients were investigated by electrocardiography, transthoracic echocardiography, 6 minutes walk test and assessment of serum NT-proBNP level. Results. Preoperatively, 23.9% of patients had HFrEF, 24.8% - HFmrEF and 51.3% - HFpEF. Analyzing the evolution of the HF phenotype in the early postoperative period, we found that most patients remained in the same group. However, among patients with preoperative HFmrEF, in 22.2% of patients there was an increase in LV EF over 50% and in 22.2% of patients was determined a reduced LV EF, p&lt;0.001. The most obvious positive dynamic of the HF phenotype was attested in patients with HFrEF, where 37% of them presented a mildly reduced LV EF postoperatively, p &lt;0.001. 78.9% of individuals with HFpEF remained in the same group, but 21% showed a decrease in LV EF, p&lt;0.001. Conclusions. At the early stage after cardiac surgery, the most positive evolution of HF phenotype was noticed in the group of patients with HFrEF. Of the 44.4% of patients with HFmrEF who switched to another HF phenotype, only a half reported an increase in LV EF over 50%. The vast majority of patients with HFpEF had the same HF phenotype postoperatively.</jats:p