CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome

Aim: To evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. Material and methods: 91 naïve gastric cancer (GC) patients were enrolled into the study. DTCs, CD8- and CD45RO-positive T lymphocytes in BM were detected using immunocytochemistry. All patients were thoroughly informed about the study that was approved by the local ethics committee. Statistical analyses were done using NCSS2000/PASS2000 and Prism, version 4.03 software packages. Results: It was detected that 80.5 and 81.3% of patients had CD8- and CD45RO-positive T cells in BM, respectively. When DTCs were detected in BM, the number of patients with CD8-and CD45RO-positive T cells in BM were 86.1 and 84.4%, respectively. It was also determined that the number of patients with DTCs in BM with categories M0 and M1 and with CD8- and CD45RO-positive T cells in BM were 86.2 and 85.7%, 85.7 and 80.0%, respectively. The association between DTCs in BM and presence of CD8 and CD45RO T cells lymphocytes in BM was not found. At the same time it was shown the association between presence of CD8 and CD45RO T lymphocytes and survival. The presence of CD8- and CD45RO-positive T cells in BM were accompanied with significantly longer overall survival of patients compared to that of patients without CD8- and CD45RO-positive T cells in BM. Conclusion: Patients with the presence of CD8- and CD45RO-posi­tive T cells in BM demonstrated better survival of GC patients than those with the absence of these cells in BM. It may be suggested that tumor cells in BM are controlled in a dormant state by T cells in BM, in particular by CD8-positive T cells. Key Words: CD8 T lymphocytes, CD45RO T lymphocytes, bone marrow, disseminated tumor cells, tumor hypoxia, survival

Bioenergetic status and hypoxia in Lewis lung carcinoma assessed by 31P NMR spectroscopy: correlation with tumor progression

Aim: Тo evaluate the hypoxia level and some indices of Lewis lung carcinoma energy metabolism by means of 31Р NMR spectroscopy in perchloric acid (PCA) tissue extracts during growth of primary tumor and metastasis. Мaterials and Methods: C57Bl/6 mice-bearing Lewis lung carcinoma were used in this study. Tumor energy metabolism was studied by 31P NMR spectroscopy and the metabolic NMR ratios were used as parameters for metabolic status and hypoxia level. Results: It was shown that growth of primary tumor is accompanied with increase of Pi/PCr, Pi/bNТP and PME/bNТP ratios that reflect drop of tumor energy status and oxygenation level in tumor tissue. These changes in relevant metabolic ratios correlate with enlargement of primary tumor volume (r = 0.87, p = 0.0045; r = 0.90, p = 0.0012; r = 0.764, p = 0.05, respectively) as well as with the number of lung metastases (rs = 0.761, p = 0.028; rs = 0.86, p = 0.0049; rs = 0.77, p = 0.040, respectively). Conclusion: In present study it was shown that 31Р NMR spectroscopy of PCA tumor tissue extracts may be used as reliable method for the assessment of the level of oxygenation as well as changes in energy metabolism in the experimental tumors. It may be helpful to evaluate the energy status of human tumors by investigation both of biopsy and surgical specimens. Hypoxia and hypoxia-associated metabolic events in primary tumor are linked with malignant progression, in particular metastasis.Цель: определить уровень гипоксии и некоторые показатели энергетического метаболизма карциномы легкого Льюис с помощью 31Р ЯМР-спектроскопии перхлорных (РСА) экстрактов ткани в процессе роста первичной опухоли и ее метастазировании. Мaтериалы и методы: использовали в исследовании мышей C57Bl/6 с перевивной карциномой легкого Льюис. Энергетический метаболизм опухоли изучали с помощью ЯМР спектроскопии, oтношения фосфорсодержащих метаболитов использовали в качестве параметров метаболического статуса и уровня гипоксии. Результаты: установлено, что рост первичной опухоли сопровождается увеличением соотношений Pi/PCr, Pi/βNТP and PME/βNТP в опухоли, что отражает снижение уровня биоэнергетического статуса и уровня оксигенации в опухоли. Эти изменения соотношений важных метаболических показателей коррелируют с увеличением объема первичной опухоли (r = 0,87, p = 0,0045; r = 0,90, p = 0,0012; r = 0,764, p = 0,05 соответственно) и количеством метатазов в легких (rs = 0,761, p = 0,028; rs = 0,86, p = 0,0049; rs = 0,77, p = 0,040 соответственно). Выводы: установлено, что 31Р ЯМР-спектроскопия PCA тканевых экстрактов может быть надежным методом оценки уровня оксигенации и биоэнергетического статуса экспериментальных опухолей. Этот метод может быть полезным при оценке энергетического метаболизма опухолей человека, в частности при исследовании биопсийного и операционного материала. Гипоксия и гипоксия-ассоциированные изменения метаболизма в первичной опухоли связаны со злокачественной прогрессией, в частности с метастазированием

Nanohyperthermia of malignant tumors.i. lanthanum-strontium manganite magnetic fluid as potential inducer of tumor hyperthermia

Objectives: To synthesize magnetic particles of lanthanum-strontium manganite, prepare the magnetic fluid (MF), evaluate the generation of heat by particles and determine their common toxiсity. Methods: Nanoparticles based on the solid solutions of lanthanum-strontium manganite (La1-xSrxMnO3) have been synthesized by a sol-gel method. Conventional methods of experimental oncology were used. Results: Nanoparticles of ferromagnetic materials on the basis of solid solutions of lanthanum strontium manganite by sol-gel method were synthesized. It was shown the possibility to regulate the aggregate form of particles that are formed during the synthesis. Magnetic fluid based on the synthesized nanoparticles and water solutions of agarose have been produced. It was shown the possibility to heat this magnetic fluid up to 42–45 °С in externally applied alternating magnetic field (AMF) operated at 100–400 kHz. It was determined that under long-term influence of AMF nanofluid is heated up to temperature which is not over that of magnetic phase transition. It was detected that magnetic powder as well as fluid have not displayed acute toxicity or side effects (intraperitoneal or intratumoral administration) in animals either intact or with transplanted tumors. Conclusions: Possibility of synthesized magnetic fluid to generate heat in externally applied AMF as well as lack of side effects allow to consider its as a potential mean for tumor hyperthermia (HT)

Direct simulation Monte Carlo for new regimes in aggregation-fragmentation kinetics

We revisit two basic Direct Simulation Monte Carlo Methods to model aggregation kinetics and extend them for aggregation processes with collisional fragmentation (shattering). We test the performance and accuracy of the extended methods and compare their performance with efficient deterministic finite-difference method applied to the same model. We validate the stochastic methods on the test problems and apply them to verify the existence of oscillating regimes in the aggregation-fragmentation kinetics recently detected in deterministic simulations. We confirm the emergence of steady oscillations of densities in such systems and prove the stability of the oscillations with respect to fluctuations and noise.Comment: 19 pages, 2 figures, 4 table

Nanohyperthermia of malignant tumors. II. In vivo tumor heating with manganese perovskite nanoparticles

Objectives: To evaluate the ability of manganese perovskite nanoparticles (lanthanum-strontium manganite) to heat the tumor tissue in vivo under action of external alternating magnetic field. Materials and Methods: The magnetic fluid on the basis of nanoparticles of perovskite manganite was tested in the heating experiments using of alternating magnetic field of frequency 300 kHz and amplitude 7.7 kA/m. Guerin carcinoma was transplanted into the muscle of rat. Magnetic fluid was injected intramuscularly or intratumorally. Temperature was measured by copper-constantan thermocouple. Results: Temperature of magnetic fluid was increased by 56 °C for 10 min of alternating magnetic field action. Administration of magnetic fluid into the muscle followed by alternating magnetic field resulted in the elevation of muscle temperature by 8 °C after 30 min post injection. Temperature of the tumor injected with magnetic fluid and treated by alternating magnetic field was increased by 13.6 °C on the 30 min of combined influence. Conclusion: In vivo study with rat tissue has demonstrated that magnetic fluid of manganite perovskite injected in the tumor increases the tumor temperature under an alternating magnetic field. Obtained results emphasize that magnetic fluid of manganite perovskite can be considered as effective inducer of tumor hyperthermia

MgZnO/AlGaN heterostructure light-emitting diodes

We report on p-n junction light-emitting diodes fabricated from MgZnO/ZnO/AlGaN/GaN triple heterostructures. Energy band diagrams of the light-emitting diode structure incorporating piezoelectric and spontaneous polarization fields were simulated, revealing a strong hole confinement near the n-ZnO/p-AlGaN interface with a hole sheet density as large as 1.82x10(13) cm(-2) for strained structures. The measured current-voltage (IV) characteristics of the triple heterostructure p-n junctions have rectifying characteristics with a turn-on voltage of similar to3.2 V. Electron-beam-induced current measurements confirmed the presence of a p-n junction located at the n-ZnO/p-AlGaN interface. Strong optical emission was observed at similar to390 nm as expected for excitonic optical transitions in these structures. Experimental spectral dependence of the photocurrent confirmed the excitonic origin of the optical transition at 390 nm. Light emission was measured up to 650 K, providing additional confirmation of the excitonic nature of the optical transitions in the devices

Studies of minority carrier diffusion length increase in p-type ZnO : Sb

Minority electron diffusion length was measured in p-type, Sb-doped ZnO as a function of temperature using the electron beam induced current technique. A thermally induced increase of electron diffusion length was determined to have an activation energy of 184 +/- 10 meV. Irradiation with a low energy (5 kV) electron beam also resulted in an increase of diffusion length with a similar activation energy (219 +/- 8 meV). Both phenomena are suggested to involve a Sb-Zn-2V(Zn) acceptor complex. Saturation and relaxation dynamics of minority carrier diffusion length are explored. Details of a possible mechanism for diffusion length increase are presented