Experimental substantiation of the use of hydroxyapatite - tricalcium phosphate bioceramics for replacing bone defects after tumor removal.

BACKGROUND: Recently, bioactive ceramics based on hydroxyapatite (HAP) and tricalcium phosphate (TCP) have been preferred as implants in bone engineering. AIM: To study bone regeneration under conditions of filling metaphyseal defects with the original HAP-TCP composition. MATERIALS AND METHODS: The experiment was carried out on inbred rats, the observation period was 2, 4, 8 weeks. Morphological studies were carried out using light and electron microscopy. RESULTS: In the dynamics of observation at 2, 4 and 8 weeks, a gradual arrangement of osteoclasts and osteoblasts on the surface of HAP-TCP was recorded, which indicates its high biocompatibility with bone tissue. During the experiment, the processes of resorption of implants, mineralization, proliferation of cellular elements of collagen and osteogenesis (osteoblasts and osteoclasts) and the formation of mature bone tissue were recorded. CONCLUSIONS: Experimental studies of plastic bone defects proved the presence of the osteoinductive and osteointegrative effect of HAP-TCP composition, which contributes to a more dynamic uncomplicated course of reparative osteogenesis.

Treatment of large osteosarcoma in children: new approach.

AIM: To improve the treatment results of patients with locally advanced osteosarcoma with large volume using neoadjuvant chemotherapy (NACT) (ifosfamide at a dose of 18 g/ml) and planning of organ-conserving surgery by evaluating the state of tumor pseudocapsule. PATIENTS AND METHODS: A study group included 46 children aged from 7 to 18 years, mean age - 12 years. In 68% of the patients tumor volume was larger or significantly larger than 200 ml (from 27 to 2400 ml), mean tumor volume was 342 ml. All patients have been examined by X-ray radiography, CT, Doppler ultrasound. Convenient chemotherapy consisted of methotrexate at a dose of 12 g/ml, cisplatin (120 mg/ml) in combination with doxorubicin (75 mg/ml). If such chemotherapy was considered ineffective with the use of an algorithm for determination of chemotherapy efficacy, 2 cycles of chemotherapy with ifosfamide at a dose of 18 g/ml per course have been applied. At the stage of planning of organ-conserving surgery, the state of tumor pseudocapsule was analyzed. In 6 months post-operative chemotherapy was carried out with the use of methotrexate, cisplatin with doxorubicin, ifosfamide at the same doses. RESULTS: Myelotoxicity of ifosfamide treatment at a dose of 18 g/ml is comparable to that of to a course of doxorubicin + cisplatin: the depth of leucopenia was significantly higher (p < 0.05), the duration of agranulocytosis is similar after such therapies. In the study group, 69.6% patients have reached grade 3-4 pathomorphosis. Organ-conserving surgery was performed in 86.9% of the patients. Local tumor recurrence was registered in 15.2% patients of the study group. 5-year relapse-free survival was achieved in 62 ± 10% (p = 0.02), the overall 5-year survival - 76.5 ± 9% (p = 0.02). CONCLUSIONS: Introduction of ifosfamide at a dose of 18 g/ml in the treatment scheme of pediatric patients with locally advanced osteosarcoma along with individualization of pre-operative chemotherapy, pre-operative analysis of NACT efficacy and the state of tumor pseudocapsule during planning stage of organ-conserving surgery significantly improves efficacy of the therapy in patients with large tumor volume.

[Results of a combined therapy of patients with metastatic bone diseases].

In the department of bone and soft tissue tumors of Institute of oncology the authors performed a combined treatment (surgery + combined chemotherapy + bisphosphonates + radiation) in 20 patients with bone metastases. Results showed that postoperative complications were observed in 2 patients, new bone lesions in 4 patients. Those satisfactory results prove the efficacy of these treatment options.

The sensitivity of chemioresistant human tumor explants to lysis by activated and nonactivated autological lymphocytes: a pilot study.

AIM: The comparative study of antitumor action of peripheral blood lymphocytes (PBL) and lymphokin-activated killer cells (LAK) on autologous cell of chemoresistant and chemosensitive human soft tissue sarcomas and tumors of epithelial origin. MATERIALS AND METHODS: Tumor explants (15 samples of soft tissue sarcomas, 10 samples of cervical and ovarian carcinomas) were cultivated with autologous lymphocytes in double diffusion chambers. Evaluation of the results was done on the basis of morphological criteria of explants growth. RESULTS: The results have shown that in the patients with the resistant soft tissue sarcomas and carcinomas LAK possess more pronounced antitumor action, than non-activated lymphocytes, whilst PBL possess higher antitumor action on sensitive epithelial tumors than that on soft tissue sarcoma. CONCLUSION: LAK possess antitumor action toward chemoresistant tumors of different origin and localization.

[Long-term results of treatment of patients with bone tumors using hydroxyapatite and calcium phosphate ceramic implants]. / Viddaleni rezul'taty likuvannia khvorykh z pukhlynamy kistok z vikorystanniam keramichnykh implantativ na osnovi gidroksylapatytu ta trykal'tsiifosfatu.

On the basis of experimental-and-clinical investigations it has been found out that the home-produced hydroxylapatite (HA)- and tricalciumphosphate(TCP)-based ceramic material is capable owing to specificities of its chemical structure and osteoinductive action of stimulating the reparative osteogenesis and is accompanied by angiogenesis. No ill effects have been noted in its use in bone plastic surgery. An apparent clinical effect has been shown to occur in postsurgical patients (n = 120) presenting with giant cell tumour, benign tumours and tumour-like affections of the bones, with the expediency having been ascertained of employment of the HA- and TCP-base ceramic material in the treatment of the above patients. The use of the above materials implants versus allotransplants promotes decline in the percentage of complications (1.66 vs 27.2), shortening of time of medical rehabilitation of patients by two to three months as compared to allotransplantation as well as hospital stay duration (by 10 to 12 days).

[Experimental studies on the effect of ceramic materials on cellular and humoral immunity]. / Eksperymental'ni doslidzhennia vplyvu keramichnogo materialu na reaktsiï klitynnogo ta gumoral'nogo imunitetu.

It has been established in an experimental setting in laboratory animals through testing a number of reactions such as active skin anaphylaxis reaction, mast cell degranulation reaction, specific leucocyte lysis reaction, delayed hypersensitivity reaction, and graft-versus-host reaction that ceramic preparations hydroxilapatite M and osteogel-7 have no sensitizing effects; osteogel-7 is not endowed with immunomodulating activity, which fact suggests to us its immunological inertness.

[Thymus endocrine function and the immune system indices of cancer patients after neutron and gamma therapy]. / Endokrinnaia funktsiia timusa i nekotorye pokazateli sostoiannia immunnoi systemy onkologicheskikh bol'nykh posle neitronnoi i gamma-terapii.

Patients with head and neck and locomotor system tumors received neutron therapy in the total doses of 4-8 and 12-14 Gy which was followed by a pronounced dose-dependent decrease in the serum thymus factor and total blood-lymphocyte levels. The latter changes were predominantly due to a decrease in the non-T-non-B cell concentration. Following the treatment, a rise in the level of circulating immune complexes and those of IgA and IgG was observed. Changes in the immune system proved less apparent in patients with locomotor system cancer who had been given 20 Gy of gamma-ray radiation.

[The combination treatment of malignant bone tumors using fast neutrons]. / Kombinirovannoe lechenie zlokachestvennykh novoobrazovanii kostei s ispol'zovaniem bystrykh neitronov.

The study deals with results of a clinical trial evaluating treatment efficacy of a 6 MeV neutron beam produced by Y-120 cyclotron (Kiev). Procedures of preoperative radiotherapy and radical treatment are discussed. Radiotherapy was administered to 52 patients suffering chondrosarcoma (30 cases), osteogenic sarcoma (15) or chordoma (7). Combined treatment (radiation + surgery) was given to 22 patients whereas neutron beam therapy--to 30. All patients with osteogenic sarcoma received adjuvant combination chemotherapy. Three-year survival rate was compared to that observed in controls in whom combined treatment had included gamma-therapy. A significant increase in three-year survival rate was observed for osteogenic sarcoma and chordoma whereas for chondrosarcoma the improvement in survival proved insignificant. The use of fast neutrons in combined treatment of bone tumors was considered promising.

[Effects of recombinant interleukin-2 on several characteristics of functional activity of lymphocytes from the lymph nodes regional to tumor and mononuclear cells of peripheral blood in cancer patients]. / Vliianie rekombinantnogo interleikina-2 na nekotorye osobennosti funktsional'noi aktivnosti limfotsitov regionarnykh k opukholi limfaticheskikh uzlov i mononuklearnykh kletok perifericheskoi krovi onkologicheskikh bol'nykh.

The level of endogenous production of IL-2 by lymphocytes of lymph nodes regional to tumour and by mononuclear cells of peripheral blood, proliferative response of these cell to recombinant IL-2, as well as a modifying influence of autologous serum and actively proliferating bioptats of autologous tumours on enumerated parameters have been studied in cancer patients (tumours of the head and neck and locomotor system). Regional IL-2-dependent immunotherapy of malignant tumors with obligatory preliminary testing for individual sensitivity of the tumor bioptat to the influence of the RIL-2 and RIL-2 activated lymphocytes is shown to be promising.

[Fast neutrons in the treatment of soft tissue sarcomas]. / Bystrye neitrony pri lechenii sarkom miagkikh tkanei.

Results of treatment of 101 cases of soft tissue sarcoma are presented in the paper. Preoperative irradiation technique and radical program of treatment are described. Combined radiation and surgical treatment was given to 45 patients whereas conservative--to 56. Sixty-three cases received adjuvant combination chemotherapy. Response and three-year survival rates were compared to those in control group treated by photons. The results observed in patients of combined and conservative treatment groups who had been irradiated with fast neutrons proved significantly better than in controls. These data suggest vistas in application of fast neutron irradiation for the treatment of soft tissue sarcomas.

[Modifying effect of the blood serum from patients with soft-tissue sarcomas on interleukin-2 production and activity]. / Modifitsiruiushchee vliianie syvorotki krovi bol'nykh sarkomami miagkikh tkanei na produktsiiu i aktivnost' interleikina-2.

Interleukin-2 (IL-2) production by lymphocytes of a peripheral blood (LPB) in patients with soft tissue sarcomas is considerably lower in comparison with that in donors. Autological serum had either suppressive or stimulative effect on LPB IL-2 production in the observed patients. The investigated serum affected LPB of donors in the same way. Serum of patients with soft tissue sarcomas had the same dual effect on the ability of the active drug IL-2 to proliferate human T-lymphoblasts. Moreover serum-inhibitors of production acted as IL-2 activity stimulators, while serum-stimulators of IL-2 production inhibited the mediator effects.

[Isolation of viable human tumor cells and their characteristics during culturing in diffusion chambers]. / Poluchenie zhiznesposobnykh opukholevykh kletok cheloveka i ikh kharakteristika pri kul'tivirovanii v diffuzionnykh kamerakh.

Methodical approaches for obtaining the viable tumour cells from solid human tumours are developed. Combination of the short-term enzymatic treatment of the tumour tissue pieces and their gradual rubbing through the metal sieve with the decreasing pore sizes permitted obtaining a large number of isolated tumour cells with the high percentage of viability.

[Production of interleukin-2 by peripheral blood lymphocytes from patients with soft tissue sarcomas]. / Produktsiia interleikina-2 limfotsitami perifericheskoi krovi bol'nykh sarkomami miagkikh tkanei.

Interleukin-2 (IL-2) production of phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) was studied in 9 healthy subjects and 19 patients with soft tissue sarcomas. Mean IL-2 production by PBL in 19 patients was significantly diminished as compared with the control. Surgery leads to an increase of IL-2 production, however, the levels observed in the control do not restore completely.