Abstract:The relationship between 5-year survival and the mean number of circulating lymphocytes during 1 month after beginning a combined therapy was investigated in 175 patients with advanced epithelial ovarian cancer to understand why myelosuppression caused by a cytotoxic treatment is almost inseparable from its benefit. Patients received a combined therapy consisting of primary cytoreductive surgery followed by different systemic treatments according to three schemes: conventional chemotherapy with cisplatinum and cyclophosphanum (CP), conventional chemotherapy with paclitaxel and carboplatinum (TP), or lower-half body irradiation (LHBI). The TP scheme included premedication with dexamethasone. The LHBI involve irradiation with a total dose of 9 Gy (3 Gy daily) in patients with primary disease. LHBI with a total dose of 1 Gy (0.1 Gy daily) was used for patients with primary disease or relapse. The LHBI treatment included five final courses of thiophosphamide/5-fluorouracil for patients with primary cancer or conventional local radiotherapy up to a total dose of 30 Gy (2 Gy daily) for relapsed patients. Survival curves were analyzed by exponential approximation, and 5-year exponential mortality rates were calculated. The mortality rates were compared with the relative decline in the mean number of circulating lymphocytes after 1 month of therapy. If pretreatment lymphocytopenia did not exceed 0.7 10 9 cells /L, a linear dependency of the exponential death rate from the relative deviation of cells in the range of 1.16 to 0.7 (p < 0.001) was observed. The inevitable side effect of cytotoxic cancer therapy in the form of lymphocytopenia sheds doubt on the actual existence of effective antineoplastic immunity; however, it provides a logical background of the morphogenic function of some circulating mononuclear cells in relation to proliferating tissues, including malignant tissues.

Data extracted from the γ Beagle Dog Tissue Archive hosted by the Woloschak Laboratory (Chicago, IL, USA) were used in a retrospective comparative study of the influence of associated morbidities on the ability of organisms to regenerate hematopoietic cells. There were 209 dogs that had been subjected to whole-body irradiation from a cobalt 60 source from 1.1 years of age until death, with dose rates of 0.003-0.038 Gy/day. One hundred fifty-six nonirradiated dogs served as controls. The presence of neoplasms clinically recorded during each dog's lifetime (uncertain benign or malignant nature) was used to assign experimental subjects and controls to one of two groups: W (with) and WO (without) lesions. Differences between the two groups were noted, mainly a longer average life span and a prevalence of solid malignancy over malignant hematopoiesis in both irradiated and nonirradiated W dogs. We propose an interpretation of these data as showing variability of the activity of tissue-committed hematopoietic stem cells, reflected not only by an increased incidence of solid benign and malignant tumors, but also by greater marrow radioresistance and a stronger viability of W cohorts.

The goal of this study was to evaluate the influence of natural variation in the regenerative status of dog tissues on the signs of hormesis, which are evident after total body exposure to low daily doses of external gamma radiation throughout the lifespan. Ninety beagle dogs of both sexes were irradiated with cobalt 60 at 0.003 Gy/day commencing 1 year after birth to death. Control (n = 169) and irradiated animals underwent whole-life clinical observation and autopsy, and were then retrospectively divided into two subgroups with (W) or without benign tumors or tumors of unknown nature (WO) that were clinically recorded on single days throughout the lifespan. Radiation hormesis was only detected in subgroup WO, which had life span (LS) of 10.7 years in the absence of radiation. The radiogenic prolongation of life to 11.8 years in the WO subgroup (p < 0.05) was similar to that in the W control and irradiated W subgroups (11.8 and 11.5 years, respectively). The number of solid malignancies found upon autopsy of the control WO subgroup was less (39.5%) than that evident in the control W subgroup (60%). Compared to the irradiated W subgroup, irradiation of the WO subgroup was accompanied by a slight increase (1.14-fold) in the number of solid malignancies evident at autopsy and in the clinical signs of tissue atrophy and body weight loss (2.4-fold and 2.4-fold, respectively), but was accompanied by strong reductions in the extent of anemia and hemoblastoses (>10-fold for both). The data exclude the notion that radiation is associated with healing, but suggest that certain pathologies (e.g., hemoblastoses) may be substituted with other less dangerous somatic diseases in weaker animals only.

Российский научный центр радиологии и хирургических технологий Минздрава РФ, Санкт-Петербург, Российская Федерация Соотношения субпопуляционного состава мононуклеарных клеток крови у 68 пациентов исследованы методом проточной цитометрии до и в течение первого месяца после трансплантации трупной печени с целью определения их возможного вклада в процессы приживления трансплантата. Полученные данные позволяют рассматривать изменения регуляторных Т-клеток после трансплантации как час-тный случай генерализованного смещения всего дифференцировочного процесса в лимфоцитопоэзе, начиная со стволовых гемопоэтических клеток и прелимфоцитов. Смещение сопровождается увели-чением юных гематопоэтических стволовых клеток, клеток предшественников лимфоцитарного ряда, клеток с ангиогенными свойствами и уменьшением большинства более зрелых дифференцирован-ных форм лимфоцитов. Ослабление «толерогенной» активности печени у больных в листе ожидания трансплантации печени и восстановление ее после трансплантации объяснено морфообразующим, трофическим механизмом. Основу этого механизма составляет увеличение в крови стволовых гемо-поэтических клеток и ангиогенных клеток, переносящих регенераторную информацию к трансплан-тату.Ключевые слова: трансплантация печени, лимфоциты, стволовые клетки, кинетика, дифференцировка клеток, морфогенез. FEATURES OF SUBPOPULATION COMPOSITION OF BLOOD LYMPHOCYTES IN RECIPIENTS WITHIN THE FIRST MONTH AFTER LIVER TRANSPLANTATION A.N. Shoutko, O.A. Gerasimova, L.P. Ekimova, F.K. Zherebtsov, A.M. Granov Russian Scientifi c Center for Radiology and Surgical Technologies of the Ministry of Healthcare of the Russian Federation, St-Petersburg, Russian FederationRatios of subpopulations of mononuclear blood cells in 68 patients were registered by method of fl ow cytometry during one month before or after transplantation of a cadaveric liver with the aim of a comparative assessment of the contribution of cellular factors into graft acceptance. Results. The obtained data allow considering the changes of separate Treg subpopulation after transplantation as a partial outcome of generalized shift of the whole process of lymphocytes differentiation, involving hematopoietic stem cells and prelymphocytes. This shift is followed by an increase of young hematopoietic stem cells, precursors of lymphocytes, angiogenic cells, and by a concomitant reduction of the majority of more matured subpopulations of lymphocytes. Conclusion. Diminishment of «tolerogenic» liver activity of before transplantation and its restoration after the organ's replacement is explained by morphogenic/trophic mechanism. The basis of this mechanism is an increase in blood of hematopoietic stem cells and other cells transferring angiogenic and regenerative information to the graft.