Предиктивная и прогностическая значимость явления потери гетерозиготности в генах ABC-транспортеров в опухоли молочной железы

ABC-transporter family genes have been well studied and their involvement in the development of drug resistance has been assessed. The presence of aberrant conditions in these genes can affect the treatment and prognosis of the disease. Loss of heterozygosity (LOH) is one of these conditions; it is a common event in cancer development. Therefore, the aim of this study was to investigate the relationship between LOH in ABC transporter genes in breast cancer and response to chemotherapy and disease prognosis. Material and Methods. A total of 130 breast cancer patients were included in the study. Microarray analysis was performed on Affymetrix CytoScan™ HD Array high-density DNA chips to assess LOH status. Chromosome Analysis Suite 4.1 software (Affymetrix, USA) was used to process microarray results. Results. Forty-nine ABC transporter genes were evaluated for LOH. The frequency of LOH ranged from 6.9 % to 90 %. An association analysis identified two genes: ABCG5 and ABCG8, in which the presence of LOH was associated with a lack of objective response to neoadjuvant chemotherapy. The presence of LOH in the ABCA5, ABCA6, ABCA8, ABCA9, ABCA10 and ABCC3 genes was associated with high rates of metastasis-free survival (log-rank test, p<0.04). conclusion. The presence of loss of heterozygosity in the ABC transporter genes was found to have no significant effect on the response to chemotherapy. However, a high prognostic potential of ABCA family genes was found

ВЛИЯНИЕ ТРАНСКРИПЦИОННЫХ ФАКТОРОВ, VEGF И ПРОТЕИНАЗ НА прогрессирование РАКА ПОЧКИ

Introduction. The efficacy of anticancer treatment depends on biological factors of tumor.The aim of the study was to determine the activity of proteasomes and calpains and to  reveal their association with VEGF, HIF-1α and NF-κΒ expressions in normal, primary and metastatic renal cell carcinoma (RCC) tissues.Methods. Ninety-three patients with renal cell carcinoma were included into the study. The expression levels of transcription factor and VEGF were measured using ELISA kits. The  levels of proteasome subunits were measured by Western Blotting. Proteasome and calpain  activities were determined using specific fluorogenic  substrates.Results. We revealed inactivation of proteolysis in patients with kidney cancer. Disease advance was associated with a significant depression of cellular proteolysis and increase in  transcription and growth factor levels in primary kidney cancer tissues. The proteolysis  activation was found in metastatic tissues.Conclusions. Our results suggest that NF-κΒ, HIF-1α and VEGF transcription factors and intracellular proteolytic systems are involved in kidney cancer progression.Введение. Эффективность противоракового лечения зависит от биологических факторов опухоли.Цель исследования – определить активность протеасом и кальпаинов и выявить их связь с содержанием  VEGF, HIF-1α и NF-κΒ в опухолевых, неизмененных и метастатических тканях карциномы почек (RCC).Материал и методы. В исследование были включены 93 пациента с почечно-клеточным раком. Содержание  транскрипционных факторов и VEGF определяли методом ИФА. Количественный состав протеасом исследовали  методом Вестерн-блоттинг. Активность протеасомы и кальпаина определяли с использованием специфического флюорогенного субстрата.Результаты. Выявлена инактивация протеолиза у пациентов с раком почки. Прогрессирование заболевания  было связано со значительным снижением уровня клеточного протеолиза и ростом содержания  транскрипционных и ростовых факторов в тканях первичной опухоли. Активация протеолиза была обнаружена в метастатических тканях.Выводы. В результате проведенного исследования показано, что факторы транскрипции NF-κΒ, HIF-1α, VEGF и внутриклеточные протеолитические системы участвуют в прогрессировании рака почки

The impact of social factors on the biological adaptation processes in children with mental retardation of psychogenic origin

The research is devoted to the study of biological adaptation of 6-7 year old children with mental retardation. We observed 187 children, including children with mental retardation into the main group (91 persons). Children whose mental development corresponded to their age were included into the control group (96 persons). It was found that children with mental retardation have some peculiarities in the course of processes of biological adaptation. They are characterized by the original functional tension of the cardiovascular system, by the predominance of sympathetic regulation pattern, a high index of strain (1.6 times higher than that of children whose mental development corresponds to their age), and by the index of functional changes. We revealed significant differences in the values of the index of functional changes at rest and after clinic orthostatic test in children with mental retardation of different origin. We noticed direct correlation between high levels of stress of regulatory systems in children with mental retardation on the one hand, and structural, psychological deformation of the family (r = 1,00), and living conditions (r = 0,76) on the other hand.Исследование посвящено изучению биологической адаптации детей 6-7 лет с задержкой психического развития. Под наблюдением находилось 187 детей, из них дети с задержкой психического развития составили основную группу (91 человек) и дети, чье психическое развитие соответствует возрасту - группа контроля - 96 человек. Установлено, что дети с ЗПР имеют некоторые особенности в течении процессов биологической адаптации, которые характеризуются изначальным функциональным напряжением со стороны сердечно-сосудистой системы, преобладанием симпатического контура регуляции, высоким индексом напряжения (в 1,6 раза выше, чем у детей чье психическое развитие соответствует возрасту) и индексом функциональных изменений. Выявлены достоверные различия в значениях индекса функциональных изменений как в состоянии покоя, так и после выполнения КОП у детей с задержкой психического развития различного происхождения. Установлена прямая корреляционная связь между высоким уровнем напряжения регуляторных систем организма детей с задержкой психического развития и структурной, психологической деформацией семьи (г=1,00), жилищно-бытовые условиями (г=0,76)

Предиктивная и прогностическая значимость явления потери гетерозиготности в генах ABC-транспортеров в опухоли молочной железы

ABC-transporter family genes have been well studied and their involvement in the development of drug resistance has been assessed. The presence of aberrant conditions in these genes can affect the treatment and prognosis of the disease. Loss of heterozygosity (LOH) is one of these conditions; it is a common event in cancer development. therefore, The aim of this study was to investigate the relationship between LOH in ABC transporter genes in breast cancer and response to chemotherapy and disease prognosis. Material and methods. a total of 130 breast cancer patients were included in the study. microarray analysis was performed on Affymetrix Cytoscantm HD Array high-density DNA chips to assess LOH status. Chromosome Analysis Suite 4.1 software (Affymetrix, USA) was used to process microarray results. Results. Forty-nine ABC transporter genes were evaluated for LOH. the frequency of LOH ranged from 6.9 % to 90 %. an association analysis identified two genes: ABCG5 and ABCG8, in which the presence of LOH was associated with a lack of objective response to neoadjuvant chemotherapy. the presence of LOH in the ABCA5, ABCA6, ABCA8, ABCA9, ABCA10 and ABCC3 genes was associated with high rates of metastasis-free survival (log-rank test, p&lt;0.04). Conclusion. The presence of loss of heterozygosity in the ABC transporter genes was found to have no significant effect on the response to chemotherapy. However, a high prognostic potential of ABCA family genes was found.Гены семейства ABC-транспортеров хорошо изучены, оценено их влияние на формирование лекарственной устойчивости. Показано, что наличие аберрантных состояний в этих генах может влиять на лечение и прогноз заболевания. Одним из таких состояний является потеря гетерозиготности (LOH), которая часто встречается в опухолевых клетках. Цель исследования ‒ изучение связи потери гетерозиготности в генах ABC-транспортеров в опухоли молочной железы с эффектом химиотерапии и прогнозом заболевания. Материал и методы. В исследование было включено 130 больных раком молочной железы. Для оценки статуса LOH был проведен микрочиповый анализ на ДНК-чипах высокой плотности Affymetrix Cytoscantm HD Array. Для обработки результатов микрочипов использовалось программное обеспечение Chromosome Analysis Suite 4.1 (Affymetrix, USA). Результаты. На предмет потери гетерозиготности было оценено 49 генов ABC-транспортеров. Частота LOH варьировала от 6,9 до 90 %. Ассоциативный анализ выявил два гена ABCG5 и ABCG8, наличие потери гетерозиготности в которых было связано с отсутствием объективного ответа на неоадъювантную химиотерапию. Наличие LOH в генах ABCA5, ABCA6, ABCA8, ABCA9, ABCA10 и ABCC3 было связано с более высокими показателями безметастатической выживаемости (log-rank test, p&lt;0,04). Выводы. Было установлено, что наличие потери гетерозиготности в генах ABC-транспортеров не оказывает значительного влияния на эффективность химиотерапии. Однако был показан высокий прогностический потенциал генов семейства ABCA

Risk assessment of men, underwented myocardial infarction in young age

A retrospective analysis of 96 patient’s cards with myocardial infarction in age younger then 40 years showed, that in this sampling such risk factors as smoking, overweight, arterial hypertension and dyslipidemia are of maximum value.Ретроспективный анализ 96 историй болезни пациентов, перенесших инфаркт миокарда в возрасте до 40 лет, показал, что в этой возрастной группе наибольшее значение в развитии заболевания имеют такие факторы риска, как курение, избыточная масса тела, артериальная гипертония и дислипидемия

Evidence for the exclusive decay Bc+- to J/psi pi+- and measurement of the mass of the Bc meson

We report first evidence for a fully reconstructed decay mode of the B_c^{\pm} meson in the channel B_c^{\pm} \to J/psi \pi^{\pm}, with J/psi \to mu^+mu^-. The analysis is based on an integrated luminosity of 360 pb$^{-1} in p\bar{p} collisions at 1.96 TeV center of mass energy collected by the Collider Detector at Fermilab. We observe 14.6 \pm 4.6 signal events with a background of 7.1 \pm 0.9 events, and a fit to the J/psi pi^{\pm} mass spectrum yields a B_c^{\pm} mass of 6285.7 \pm 5.3(stat) \pm 1.2(syst) MeV/c^2. The probability of a peak of this magnitude occurring by random fluctuation in the search region is estimated as 0.012%.Comment: 7 pages, 3 figures. Version 3, accepted by PR

Top quark mass measurement using the template method at CDF

We present a measurement of the top quark mass in the lepton+jets and dilepton channels of $t\bar{t}$ decays using the template method. The data sample corresponds to an integrated luminosity of 5.6 fb$^{-1}$ of $p\bar{p}$ collisions at Tevatron with $\sqrt{s}=1.96$ TeV, collected with the CDF II detector. The measurement is performed by constructing templates of three kinematic variables in the lepton+jets and two kinematic variables in the dilepton channel. The variables are two reconstructed top quark masses from different jets-to-quarks combinations and the invariant mass of two jets from the $W$ decay in the lepton+jets channel, and a reconstructed top quark mass and $m_{T2}$, a variable related to the transverse mass in events with two missing particles, in the dilepton channel. The simultaneous fit of the templates from signal and background events in the lepton+jets and dilepton channels to the data yields a measured top quark mass of $M_{top} = 172.1 \pm 1.1(stat) \pm 0.9(syst).$Comment: submitted to Phys. Rev.

Measurement of WγW\gamma and ZγZ\gamma Production in ppˉp\bar{p} Collisions at s\sqrt{s} = 1.96 TeV

The Standard Model predictions for $W\gamma$ and $Z\gamma$ production are tested using an integrated luminosity of 200 pb$^{-1}$ of \ppbar collision data collected at the Collider Detector at Fermilab. The cross sections are measured selecting leptonic decays of the $W$ and $Z$ bosons, and photons with transverse energy $E_T>7$ GeV that are well separated from leptons. The production cross sections and kinematic distributions for the $W\gamma$ and $Z\gamma$ are compared to SM predictions.Comment: 7 pages, 4 figures, submitted to PR

Measurement of the Lifetime Difference Between B_s Mass Eigenstates

We present measurements of the lifetimes and polarization amplitudes for B_s --> J/psi phi and B_d --> J/psi K*0 decays. Lifetimes of the heavy (H) and light (L) mass eigenstates in the B_s system are separately measured for the first time by determining the relative contributions of amplitudes with definite CP as a function of the decay time. Using 203 +/- 15 B_s decays, we obtain tau_L = (1.05 +{0.16}/-{0.13} +/- 0.02) ps and tau_H = (2.07 +{0.58}/-{0.46} +/- 0.03) ps. Expressed in terms of the difference DeltaGamma_s and average Gamma_s, of the decay rates of the two eigenstates, the results are DeltaGamma_s/Gamma_s = (65 +{25}/-{33} +/- 1)%, and DeltaGamma_s = (0.47 +{0.19}/-{0.24} +/- 0.01) inverse ps.Comment: 8 pages, 3 figures, 2 tables; as published in Physical Review Letters on 16 March 2005; revisions are for length and typesetting only, no changes in results or conclusion

Measurement of the Helicity Fractions of W Bosons from Top Quark Decays Using Fully Reconstructed top-antitop Events with CDF II

We present a measurement of the fractions F_0 and F_+ of longitudinally polarized and right-handed W bosons in top quark decays using data collected with the CDF II detector. The data set used in the analysis corresponds to an integrated luminosity of approximately 318 pb -1. We select ttbar candidate events with one lepton, at least four jets, and missing transverse energy. Our helicity measurement uses the decay angle theta*, which is defined as the angle between the momentum of the charged lepton in the W boson rest frame and the W momentum in the top quark rest frame. The cos(theta*) distribution in the data is determined by full kinematic reconstruction of the ttbar candidates. We find F_0 = 0.85 +0.15 -0.22 (stat) +- 0.06 (syst) and F_+ = 0.05 +0.11 -0.05 (stat) +- 0.03 (syst), which is consistent with the standard model prediction. We set an upper limit on the fraction of right-handed W bosons of F_+ < 0.26 at the 95% confidence level.Comment: 11 pages, 2 figures, submitted to Phys. Rev.