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Expression of the mutant protein-suppressor of tumor growth p53 and the receptor of epidermal growth factor of type II--HER-2/neu may serve as prognostic factors for patients with chondrosarcoma of malignancy grade II. Combined expression of these proteins in the tumor tissue correlates with shorter 5-year survival of recurrence-free patients. The data obtained may be used for prognosis of chondrosarcoma course and choice of adequate therapy.

Phase-I clinical studies of teraphtal and a "teraphtal + ascorbic acid" catalytic system have been completed. The dose-limiting toxicity and maximum tolerable dose were not reached even at the end of maximal dose trials. No side-effects characteristic of antitumor cytostatic drugs were registered. The gravest side-effect ever recorded was a collapse which could not be linked to teraphtal dosage and was probably caused by hypersensitivity to the drug. The drug was recommended for phase II trials.

Expression of urokinase- and tissue-type plasminogen activators and their inhibitor PAI-1 in the cytosolic fraction of 20 osteosarcomas, 20 chondrosarcomas, 13 giant-cell bone tumors, 5 Ewing's sarcomas, and 7 osteochondral exostoses was studied by enzyme immunoassay. The content of urokinase-type plasminogen activator increased, while the concentration of tissue-type plasminogen activator decreased in bone tumors of various histological compositions compared to osteochondral exostoses. A positive correlation was found between PAI-1 content and the volume of osteo- and chondrosarcomas. Expression of urokinase-type plasminogen activator increased in patients with primary osteosarcomas characterized by early generalization of the pathological process.

The content of urokinase- and tissue-type plasminogen activators and plasminogen activator inhibitor PAI-1 in the cytosol of primary and metastatic melanomas and benign skin pigment neoplasms was estimated by enzyme immunoassay. It was shown that local growth and invasion of melanomas are related to suppressed expression of tissue plasminogen activator. The content of urokinase plasminogen activator increases in patients with distant metastases and large thickness of the primary tumor.

This paper presents results of comparative enzyme immunoassay of soluble serum Fas antigen (sFas) in 98 patients with benign and malignant bone tumors, 15 patients with mechanical bone traumas, and 60 normal individuals of compatible age. The prevalence and concentration of sFas were significantly greater in patients with bone tumors than in normal donors and patients with mechanical bone traumas. The association of sFas with the pathogenesis of primary bone tumors is discussed in the paper.

Serum contents of leptin and soluble Fas antigen were measured in 28 patients with osteosarcoma, 7 with neuroectodermal bone tumors, and 17 healthy subjects. The incidence and levels of soluble Fas antigen in patients with osteosarcoma and neuroectodermal bone tumors were higher than in healthy subjects and did not depend on sex and age in both healthy subjects and patients. Serum concentration of leptin in women was higher than in men (both in healthy controls and patients) and was lower in healthy subjects compared to patients with osteosarcoma and neuroectodermal bone tumors. A trend to a negative correlation between the concentrations of leptin and soluble Fas antigen in female patients with osteosarcoma and male patients with neuroectodermal bone tumors was revealed. The role of leptin and soluble Fas antigen in the pathogenesis of primary bone tumors is discussed.

The paper provides data of comparative assessment of activity of the key enzymes in metabolism of androgens in various morphological variants of sarcomas and benign bone tumors in 46 patients within the age range from 15 to 61, which were under treatment in the ORC named after N. N. Blokhin, RAMS, from 1996 to 1997. On the basis on publications and our own research results we can suggest that malignant human bone tumors of various histogenesis are subject to metabolic processes of testosterone (T), the principal androgen regulator in the bone tissue, as well as formation in bones of 5 alpha-dihydrotestosterone (DHT). One cannot exclude a possibility that metabolism of androgen in bone tissues is directed towards formation of other androgens (in addition to DHT), which may participate in the bone tissue regulation, for instance, 3 alpha- and 3 beta-diols; specific activity of the latter has recently been intensively scrutinized. One can expect that further research shall disclose the clinical significance of metabolism of androgens and of individual androgens in human bone formations.

The role of androgens in human normal and neoplastic bone tissues is still unclear. The paper presents data on metabolism of androgens in homogenates of malignant (osteosarcoma, chondrosarcoma, Ewing and giant cell) and benign primary tumors from 46 male and female patients aged 14-58 years. Using two substrates (testosterone and 5 alpha-dihydrotestosterone) for the first time are shown activities of main enzymes of androgen metabolism in all tumor types. 5 alpha-reductase activity was similar in all tumors, 3 alpha-hydroxysteroid dehydrogenase activity was the highest while that of 17 beta-hydroxysteroid dehydrogenase was the lowest. Unknown metabolite(s) of 5 alpha-dehydrotestosterone was discovered which may be hydroxy-metabolites of 5 alpha-androstane-3 beta, 17 beta-diol. A principal scheme of androgen metabolism in human neoplastic tissue is proposed.

Results of examination and treatment of 24 patients with primary neoplasms of the sternum including chondrosarcoma (18 cases), solitary plasmacytoma (5) and osteogenic sarcoma (1) were analysed. The diagnosis was based mainly on X-ray procedures and was further improved by computed tomography which allowed to precisely evaluate the extent of intrathoracic mass and its relation to adjacent mediastinal structures. Surgery was the main procedure used for the treatment of primary tumors of the sternum. Sixteen patients were operated on, and not a single case showed involvement of the mediastinum. Closure of defect was the major difficulty involved in the surgical treatment. Adequate resection of the sternum followed by autoplasty yielded good results.

Principles of evaluating prognosis in parosteal sarcoma were developed with respect to clinical and morphological pattern of disease and type of treatment. A mathematical model for making prognosis and a procedure for its multifactorial analysis were suggested.

Results of a prospective randomized clinical trial conducted by the WHO Collaborating Centers for the Evaluation of Methods of Diagnosis and Treatment of Melanoma are reported. Five-hundred-fifty-three Stage I patients whose limbs were affected entered the study; 267 were submitted to wide excision and immediate node dissection and 286 had wide excision and node dissection at the time clinically positive nodes were detected. Survival curves of the two treatment groups could be superimposed. No subsets of patients benefitted from immediate node dissection. The authors conclude that delayed node dissection is as effective as the immediate dissection in Stage I melanoma of the extremities if the patient can be checked every three months. If the quarterly follow-up is not guaranteed, immediate node dissection is advisable, at least for melanomas thicker than 2 mm.

553 patients with stage I malignant melanoma of the limbs entered a prospective randomized clinical trial carried out by the W.H.O. Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma from September 1967 to January 1974. 286 patients were submitted to wide excision of primary and node dissection at the time as appearance of regional lymph node metastases and 267 to wide excision and immediate node dissection. Survival was identical in the 2 groups. Different subsets of patients were evaluated to assess whether some groups of patients may benefit from immediate node dissection. As regards sex, females and a significantly higher survival rate than males (p < 0.05), but results were not improved by immediate node dissection. Maximum diameter and elevation of primary melanoma were significantly related to survival but also in these cases immediate node dissection did not achieve better results. 63 patients had an excisional biopsy of their melanoma within 4 weeks before final treatment. This procedure did not worsen survival and also in this case immediate node dissection did not improve survival. 273 cases were classified according to histologic type: survival of superficial spreading and nodular melanoma was not different at a statistically significant level after the 2 treatment modalities. 325 cases were considered classifiable according to Clark's levels, out of these 165 were submitted to immediate node dissection. Neither level III nor level IV cases showed higher survival rate after immediate node dissection. Maximum tumor thickness according to Breslow was evaluated in 338 cases: 188 were submitted to wide excision and immediate node dissection. In no clusters of thickness did the enlarged surgical procedure achieve better results. The authors conclude that there is good evidence that in stage I melanoma of the extremities delayed dissection is as effective as the immediate one in the control of the disease if the patient can be kept under strict clinical control. Immediate node dissection is advisable if the quarterly follow-up is not guaranteed, at least for melanomas thicker than 2 mm.

The effectiveness of cis-diammine-dichloroplatinum (cisplatinum, platidiam, DDP) alone or as a component of combined treatment was evaluated in 85 patients with osteogenic sarcoma. The said drugs were used as adjuvants following radical surgery (group I-18 cases), in combined treatment of solitary and single lung metastases (group 2-7 cases) and in 60 patients with advanced tumors (group 3). An analysis of long-term results showed response in 30.8% in group 3. In group 2, application of chemotherapy plus surgery was followed by remissions of 2-46+-month duration (mean-13.9 months). In group I, 78.7% are expected to survive metastasis-free more than 12 months. Toxicity was moderate, with nausea and vomiting (87.1%), myelosuppression (52.8%), nephrotoxicity (48.6%) and alopecia (75.7%) being the most common side-effects.

The results of treatment of 315 cases of osteogenic sarcoma are presented. Available methods of primary tumor therapy fail to prevent dissemination of neoplastic disease by blood circulation. However, following a prophylactic course of chemotherapy (adriamycin, vincristine, cyclophosphamide, sarcolysine), 3- and 5-year survival rates in 45 cases of limb amputation for osteosarcoma increased to 38.1% and 30.5%, respectively. No recurrences were observed in 39 patients with extensive segmental resection of bone who preoperatively received intra-arterial infusions and radiation therapy; the 3-year survival rates were a high as 43.9% and patients showed good performance. The method offers good advantages in the treatment of patients with osteogenic sarcoma.

Radical surgery was performed in 69 cases of primary and recurrent localized soft-tissue sarcomas (extended dissection of tumor--53, exarticulation or amputation--16) after a course of non-uniform irradiation, when other methods of specific treatment had failed. Areas of exposed tumors were irradiated with focal doses of 90-120 Gy, screened areas--with 40-60 Gy. Radiation was delivered through a latticed diaphragm from the same field. Postoperative complications due to intensive irradiation and radiation injury were comparable to those involved in standard radiation procedures. A 5-year survival rate was 50% (primary tumor--16 and relapse--77%).

Out of 2018 patients, skin melanoma occurred in IO2 (5%) cases during pregnancy. Three-, five- and ten year survival was analysed in the latter cases versus term of pregnancy, abortion and the stage of the disease. Also comparison was made between the said group, another 42 females who developed tumors during lactation period and 599 normally-cycling females of reproductive age who were not pregnant when melanoma appeared (controls). Significantly lower 10-year survival was observed in pregnant patients, as compared with those who were not pregnant (p less than 0.05). Five- and ten-year survivals were significantly lower in cases of stage I tumor during the latter half of pregnancy than in skin melanoma patients who were not pregnant (p less than 0.05). Abortion during the first half of pregnancy was found to produce an adverse effect on prognosis in stage I tumor patients while this effect was reversed in stage II tumor. No significant differences were found between 3-, 5- and 10-year survival in melanoma patients who had pregnancies before the disease and those who had not (p greater than 0.05).

The effect of adjuvant chemotherapy on survival and prognosis in osteogenic sarcoma versus basic clinico-roentgenomorphological characteristics of tumor was studied in 108 cases. Prognosis was found to depend on patient's age, site and size of tumor, but mainly on the roentgeno-morphological pattern of the latter. Osteolytic form appeared to have a better course in cases of adjuvant chemotherapy. This was matched by osteoplastic form requiring surgical treatment only. The results suggest a strictly differentiated approach to selection of treatment modality, particularly in cases of post-operative chemotherapy.

The main principles and the structure of the cancer control organization in the USSR are described. The trends in the incidence of selected forms of malignant tumors and regional differences in USSR are documented with statistical data.

The experience in the management of 246 patients with local osteogenic sarcoma and 67 patients with pulmonary metastases in the All-Union Oncologic Research Center, AMS USSR, is presented here. All the patients underwent surgery, but starting in 1974, various modalities of adjuvant chemotherapy (not randomized) were applied in addition. In the surgery alone group, prognosis was very poor: only 7.0% of patients survived free of disease 5 years from the primary tumor treatment. Adjuvant chemotherapy (adriamycin + vincristine + melphalan + cyclophosphamide) following amputations increased this rate to 34.0%; combining segmental resections of an affected bone with preoperative intraarterial adriamycin infusion and radiation (36 Gy) increased the rate to 35.5%. In patients with grade 4 tumor damage (tumor cells are not found upon examination of a large number of sections), the rate increased to 57.9% (P less than .05). Another regimen of adjuvant chemotherapy (platidiam or cisplatin + adriamycin + cyclophosphamide) gives a chance to 78.8% of patients to survive 1 year free of metastases. The same chemotherapy regimen enables us to achieve an objective effect in 30.8% of patients with pulmonary metastases, and its combination with surgical metastasis ablation makes it possible to obtain a complete remission, lasting from 2 to 46 months (average 13.9 months). Toxic manifestations of the chemotherapy regimens considered are moderate. Prognosis in adjuvant chemotherapy is related to age, tumor site, its local dissemination, and morphologic type of osteogenic sarcoma.

From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clark's level or Breslow's thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.

The concentrations of vascular endothelium growth factor and angiogenin were measured by enzyme immunoassay in the sera of healthy subjects and patients with osteosarcoma and Ewing's tumor with consideration for the main clinical and morphological characteristics of the diseases. The studied angiogenic factors were characterized by high individual variability in both healthy subjects and age- and sex-matched patients with primary bone sarcomas. The level of endothelial growth factor was higher in control women than in men. The highest concentration of endothelial growth factor was detected in male patients with Ewing's tumor. Possible involvement of vascular endothelium growth factor and angiogenin in the pathogenesis of osteosarcoma and Ewing's tumor is discussed.