Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Parenchymatous-stromal factors in hemoblastoses

The data available in the literature data on the role of neoangiogenesis and extracellular matrix factors in the pathogenesis of acute and chronic leukemias and lymphoproliferative diseases are presented. Hematopoiesis and endothelial cells have a common pluripotential progenitor. Angiogenic and fibroblast growth factors are involved chronic leukemia. The phenotype of lymphoid cells determines the type of the cellular and extracellular factors.     

Diagnosis of lymphoproliferative diseases by bone marrow trepanobiopsy specimens

Based on the study of 2000 bone marrow trepanobiopsy specimens from patients with different types of lymphoproliferative diseases, the authors present the incidence and specific features of specific bone marrow lesion and the state of normal hemopoiesis and stroma. They also give data of bone marrow immunohistochemical studies using a many mono- and polyclonal antibody panels. The criteria for the differential diagnosis of reactive polyclonal lymphoid proliferation in the bone marrow that may accompany many hematological and non-hematological diseases with specific bone marrow lesion in lymphoproliferative diseases are outlined. The high diagnostic value of a study of bone marrow trepanobiopsy specimens is shown in the diagnosis of lymphoproliferative diseases.     

Transplantations of allogenic and autologous hemopoietic stem cells in acute leukemia (results of 20-year experience)

AIM: To analyse results of transplantation of allogenic and autologous hemopoietic stem cells (allo-THSC and auto-THSC) with myeloablation preconditioning in patients with acute leukemia (AL) performed in 1987-2006. MATERIAL AND METHODS: A total of 71 allogenic and 45 autologous THSC were performed in 116 patients with different AL variants. Conditioning in all allo-THSC included busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). This regimen was used in 29 recipients of auto-HSC. Cyclophosphamide in a dose 120 mg/kg and total radiation of the body in a dose 12 Gy were given to 16 recipients. Overall, relapse-free and event-free survival of patients after THSC were analysed as well as early (first 100 days) and overall lethality. Auto-THSC in 15 patients was for the first time followed by immunomodulating therapy aimed at prevention of AL relapses: in acute myeloid leukemia ATRA in combination with alpha-interferon, in acute lymphoblastic leukemia (ALL)--ronkoleukin, interleukin-2 preparation. RESULTS: Overall survival of AL patients after allo-THSC for the observation period increased from 31 to 58%, early lethality fell from 44 to 4%. Results of allo-THSC conducted in the first complete remission were much better than in patients with other AL stages at the time of THSC. After auto-THSC 5-year survival rose from 22 to 60% while early lethality reduced from 33 to 4%. Administration of immunomodulating therapy after auto-THSC increases 5-year survival from 35 to 80%. CONCLUSION: Outcomes of THSC in AL has improved for the last 20 years. Outcomes of allo-THSC performed in the first complete remission are much higher. Immunomodulating therapy after auto-THSC promoted better results.     

Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non‐small cell lung cancer

Urokinase plasminogen activator (uPA) cleaves its three‐domain cell surface receptor, uPAR, liberating domain I [uPAR(I)] and leaving the cleaved uPAR(II‐III) on the cell surface. Both intact and cleaved uPAR can be shed from the cell surface. uPAR(I) was previously shown to be a prognostic factor in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non‐small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time‐resolved fluoroimmunoassays (TR‐FIAs) measuring intact uPAR(I‐III) (TR‐FIA 1), uPAR(I‐III) + uPAR(II‐III) (TR‐FIA 2) and uPAR(I) (TR‐FIA 3) were applied. The Spearman rank correlations between plasma and serum levels of uPAR(I‐III), uPAR(I‐III) + uPAR(II‐III), and uPAR(I) were 0.89, 0.94 and 0.68 respectively. Survival analysis demonstrated that high levels of all uPAR forms were associated with shorter survival. Adjusted for histological subtype high plasma uPAR(I‐III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis in NSCLC.     

The characteristics of the clinical course of lymphosarcomas when using combined therapy including splenectomy]

The authors relate the results of a clinico-morpho-instrumental analysis of the clinical course of lymphosarcomas in 38 patients with different morphological patterns of the disease with primary injury to the spleen. The patients received multimodality therapy including splenectomy. It has been established that later the short-term effect of splenectomy permits the implementation of different polychemotherapy programs, favouring a better lymphosarcoma prediction.