[en] From January 1976, 50 patients with squamous cell cancer of the head and neck were treated with telecobalt preoperative irradiation followed by appropriate surgery. Another group of 50 patients, who matched in risk factors and stage of disease, were treated with preoperative chemotherapy and surgery. Chemotherapy consisted of bleomycin, vincristine, mitolactol and methotrexate. All patients received 3 courses. Surgery was performed 2-3 weeks post-chemotherapy or 4-6 weeks post-radiotherapy. Forty four percent of the patients in the radiotherapy group showed recurrences, while 30% of the patients had recurrence in the chemotherapy group. The overall 3-year survival rate was 66% in the chemotherapy group and 57% in the radiation therapy group, with no statistical difference. (author)

[en] Seventy seven squamous cell carcinomas (10 oral cavity, 15 tongue, 26 pharynx and larynx), with different grading were analyzed for the presence of HPV DNA by in situ hybridization. Positive signals were found on the nuclei of cancer cells in 25 (32.5%), in the epithelia adjacent to squamous cell carcinomas in 2 (8.7%), and in the resected margins in 1 (4.3%) case. HPV DNA positive signals were obtained in 42% of laryngeal, 34% of pharyngeal, in 20% of oral, and 20% of tongue carcinomas. Out of 25 HPV positive carcinomas a single HPV type was detected in at least 11 (44%), and double or multiple infection in 36% cases; altogether , HPV 6 DNA was determined in 15 (60%), and HPV 16 and/or 18 DNA in 17 (68%) head and neck tumors. The detection rate of HPV was lower than of HPV 16 and/or 18 for tumors in oral cavity, tongue and larynx. Out of 25 HPV DNA positive carcinomas 21% were graded as G1, 27% as G2, and and 44% were G3. The results indicate that HPV may be involved in the pathogenesis of head and neck squamous cell carcinomas. (author)

[en] We previously found that human cervix carcinoma HeLa cell irradiated with multiple fractions of gamma rays (0.5 Gy daily, five times per week over 6 weeks) become resistant to cis--dichlorodiammine platinum(II) (cis-DDP), methotrexate (MTX) and vincristine (VCR), but retain the same sensitivity to gamma rays or UV light. In the present report attempts were made to elucidate the mechanisms by which these these cells have acquired resistance to cis-DDP and VCR. The sensitivity to different drugs was measured by modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)method. Neither buthionine sulfoximine (BSO) nor ethacrinic acid were able to reverse the resistance of preirradiated cells to cis_DDP. Therefore, neither the increased levels of glutathione nor glutathione transferase seem to be involved in resistance to cis-DDP. Resistance of preirradiated cells to vincristine was abolished by the addition of verapamil, indicating that resistance to this drug may depend on the increased expression of plasma membrane P-glycoprotein. It was concluded that mechanism of resistance of preirradiated cells to cytostatics are multi-factorial and involve at least the increased levels of metallothioneins and changes in the plasma membrane. Acquired resistance to cytotoxic drugs induced by preirradiation may be the reason for the induced response to these drugs after radiation treatment of certain tumors. (author)

[en] Sixty-three locoregional breast cancer biopsies were examined for association among epidermal growth factor receptors (as parameter of of autocrine growth control), and estrogen and progesterone receptors (as endocrine parameters of estrogen responsiveness). In the tumor group with similar steroid receptor levels, low (0-50 fmol/mg), medium (50-100 fmol/mg) and high (above 100 fmol/mg), an inverse quantitative correlation between epidermal growth factor receptors and progesterone receptors was obtained (p<0.05). In the tumor groups where estrogen receptor levels were higher or lower than progesterone receptor levels, epidermal growth factor receptors were correlated neither with estrogen nor with progesterone receptors (p>0.05). It seemed that inverse correlation between endocrine and autocrine parameters obtained in previous studies might not be a common behaviour of all breast tumors. (author)

[en] In a group of 391 patients with primary breast cancer the cytosolic concentrations of estrogen receptors (ER), protein (PS2), cathepsin (Cath-D), polypeptide specific antigen (TPS), thymidine kinase (TK) and cyclo-adenosine monophosphate (cAMP) were determined. PS2 production was found to be significantly depend not only on ER but also on cAMP. A similar dependence on ER and cAMP production was found also in Cath-D. When the production of these prognostic factors was correlated with the occurrence of metastases to axillary lymph nodes, three prognostic unfavorable groups of primary breast carcinomas were revealed. The first group was represented by tumors with negative PS2 values (=< 2.5 ng mg^-1) and elevated TPS values (>= kU mg^-1). The second group comprised prognostic very unfavorable tumors with moderately to highly elevated PS2 values and positive Cath-D values (>+35 pmol mg^-1), or positive TPS values (>+8.0 kU mg^-1). The third group was constituted by tumors with elevated TK (>=5.0 U mg^-1) and ER values (>= 40 fmol mg^-1). The possible role of PS2 in the metastasizing of primary breast carcinomas is discussed. (author)

[en] Twenty-nine bilateral breast carcinoma patients were analyzed retrospectively. The incidence of bilateral carcinoma of the breast among unilateral breast cancer patients was approximately 2.4 %. Median age was 46 years at the time of first cancer diagnosis (range 26-69 years). The majority of the lesions were invasive ductal carcinoma (86 %). Of 58 tumors, 10 were staged as Stage I (17 %) 30 as Stage II (52 %), 8 as Stage III (14 %) and 10 as Stage IV (17 %). Patients were treated with combinations of surgery, radiation treatment and chemotherapy. Of 29 patients with bilateral breast cancer, 5 presented with simultaneous bilateral disease (17 %), 7 (24 %) with synchronous tumor whereas 17 (59 %) developed asynchronous tumors. The mean interval between two cancers was 2.6+-0.6 years. Overall survival was 4.8+-0.7 years and overall 5-year actuarial survival was calculated to be 51 %. Age, menopausal status and tumor size at the time of initial cancer correlated with the time interval between two cancers. Age, tumor size and nodal status at the time of initial cancer and the time initial between two cancers correlated with the overall survival. (author)

[en] Biosynthesis of folyl derivatives derived from subcutaneously injected 2-[¹⁴C]folate was studied in Ehrlich ascites carcinoma (EAC) cells and in mouse liver and kidneys. Retention of exogenous folate was followed by measurements of the total radioactivity of folyl derivatives present in the EAC cells and organs examined. Identification of unconjugated and conjugated folyl derivatives was done by means of column chromatography on Sephadex G-25, G-15 and cellulose sheets. The level of retained radioactivity in folyl derivatives, being 5% in the liver and 1% in the kidneys of the radioactivity administered to mice, was similar in healthy and tumor-bearing animals. Moreover, no quantitative and qualitative differences were found in folyl mono- and polyglutamates originating from the organs of healthy or tumor-bearing mice although the content of folyl polyglutamates rose faster in liver and kidneys of EAC cells-bearing mice as well as in the tumor cells, than in the organs of healthy mice. (author)

[en] Using the exocolonizing test, ⁵⁹Fe utilization technique and classical cytology, 210 days after i.v. injection of 166.7 kBq of ²³⁹Pu/kg in about 30% of contaminated mice a proliferative activity was observed in vertebral bone marrow, characterized by high relative numbers of pluripotent hemopoietic stem cells, significantly higher than in the seriously damaged vertebral bone marrow of other ²³⁹Pu-treated mice and even higher than in untreated controls. Also the amount of cells in the granulocytic series increased. After transplantation to the heavily irradiated syngeneic hosts the stem cells differentiated into splenic colonies with higher iron utilization than in corresponding controls. Higher numbers of mature granulocytes were also found in the peripheral blood and the spleen. It is assumed that this activity was an inadequate reparative response of the hemopoietic stem cell compartment to the damaging effect and it is considered to be the critical phase which not only preceded the induction of granulocytic leukemia but also created conditions favorable for leukemic transformation of the hemopoietic stem cells. (author)

[en] Unlike the bovine pancreatic ribonuclease (RNase A), bovine seminal ribonuclease (BS RNase) displays various biological activities; including antitumor activity, immunosuppressivity, spermatogenicity and embryo-toxicity. To learn more about its antitumor effect we tested BS RNase on the growth of 16 cell lines derived from patients with various hematological malignancies. The cells of lymphoid origin were generally more susceptible to BS RNase, administered in the range of concentrations from 2 to 100 μg/ml, than the myeloid ones. RNase A used at the same concentrations did not exert any inhibitory effect. The inhibitory effect of BS RNase persisted in cultured cells three times wash in complete medium and cell re-cultivation in fresh medium free of BS RNase. Four cell lines were very little sensitive (KG-1 and U-937) or resistant (JOK and NAMALWA) to BS RNase regardless of their origin. The in vivo antitumor effect of BS RNase was tested on human prostate carcinoma transplanted to athymic nude mice. The daily dose of BS RNase (0.25 mg/20 g) was administered for three weeks except weekends (15 doses) by three different ways (intraperitoneally - i.p., subcutaneously - s.c. and intratumorally - i.t.). Whereas i.p. administration was ineffective, s.c. administration significantly reduced size of the tumors and i.t. administration abolished half of the tumors in treated mice. The average of treated mice decreased during the experiment by 10-15%. (author)

[en] To determine the maximum tolerated dose (MTD), and therapeutic efficacy of carboplatin (CBDCA) in combination with etoposide and bleomycin (CEB) as initial chemotherapy for poor prognosis germ cell tumors, a CBDCA dose escalation supported with GM-CSF had been performed. Twenty four untreated patients were treated with CBDCA 400 mg/m² on day 1, etoposide 100 mg/m² on days 1 to 5 and bleomycin 30 mg on days 1,3, 5. Four cycles were scheduled at 21-day interval. The first cohort of 6 patients received only initial chemotherapy regimen. In the subsequent cohorts of six patients, the CBDCA dose was increased by 100 mg?m². A fixed dose and schedule of GM-CSF at 5 μg/kg subcutaneously was given on days 6 though 15. Myelosuppression, with neutropenic fever and hemorrhages, was the dose-limiting toxicity at the 600 mg/m² dose level. The recommended dose of CBDCA is 500 mg/m². Overall complete response (CR) rate was 71% and with median follow up of 25 (16-34) months, 58% of patients are alive and have no evidence of disease (NED). A higher number of CR was achieved with CBDCA dose higher than 400 mg/m² compared with CBDCA dose of 400 mg/m² (92 vs. 50%, p=0.03), as well as a higher proportion of patients who alive and with NED (75 vs. 42%, p=0.1). Despite GM-CSF support, the MTD of CBDCA could not be increased beyond 500 mg/m² (50% of the dose escalation of the dose escalation), due to severe myelosuppression. The treatment outcomes obtained with CEB in our study are no better than the standard cisplatin-based chemotherapy. Further studies of this regimen, where CBDCA dose should be calculated according to to the patients glomerular filtration rate are warranted. (author)