[The effect of biocarbazine on the indices of humoral and cellular immunity in mice]. / Vliianie biokarbazina na pokazateli gumoral'nogo i kletochnogo immuniteta myshei.

Biocarbazin (5-3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide) when administered in different doses and schedules depressed the primary immune response of mice to erythrocytes (SE). A dose-dependent effect on the immunosuppression degree is revealed. Both the inductive and productive stages of antibody formation are sensitive to the immunosuppressive action of the agent. Under certain conditions biocarbazin induced a sharp suppression of humoral immune response. At the same time, it enhanced significantly the delayed-type hypersensitivity (DTH) response to SE.

[Effect of surgical treatment on the natural killer activity in lung cancer patients]. / Vliianie operativnogo lecheniia na aktivnost' estestvennykh killernykh kletok u bol'nykh rakom legkikh.

The NK activity was studied in 15 male patients with stage III of the lung cancer. All patients underwent operation. The NK activity was tested against H3 uridine-labeled K-562 tumour cells in the 4-hour cytotoxic test before and 8-14 days after the surgery. As control 15 healthy men were tested. The NK activity of mononuclear cells of the peripheral blood and nonadherent lymphocytes in the lung cancer patients before surgery was significantly decreased (P less than 0.001). Surgery did not affect essentially the NK activity. The removal of monocytes from the mononuclear cell suspension of the peripheral blood caused enhancement of the NK activity only in the postoperative period (P less than 0.05). Survival of the patients did not correlate with the cytotoxic activity of the NK cells before (r = 0.071) and after surgery (r = 0.275). The postoperative cytotoxic activity of NK cells correlated better with survival of the patients.

Changes in the rosette forming capacity of lymphocytes after surgery or surgery and immunochemotherapy of malignant melanoma in man.

The E-rosette forming capacity of lymphocytes was measured in 39 melanoma patients, performing the test at 4 degrees C and at 20 degrees C, prior to treatment, following surgery, and in 11 patients was carried out at three points: before and after surgery as well as after immunochemotherapy with DTIC and BCG. The results have shown a marked depression in E-rosettes at 4 degrees C and at 20 degrees C, whereas more expressed inhibition was registered at 4 degrees C. Following surgical removal there were no significant changes in the E-rosettes. After immunochemotherapy an increase of the E-rosettes was observed.

In vitro cell-mediated immune reactivity in colon cancer patients.

147 colon and/or rectum cancer patients in all clinical stages (according to TNM classification) aged 34 to 71 years were studied before radical surgery and 14, 45 and 90 days after it. The in vitro cell-mediated immunity was evaluated using the blastogenic transformation of blood lymphocytes to phytohemagglutinin (PHA), fast and total E rosettes. The immunosuppression observed in all clinical stages in comparison to donors becomes deeper 14 days after operation. 45 and 90 days after operation all three parameters studied increase but only in the clinical stage II (localized disease), the values reach and even surpass their initial level. Based on the obtained data conclusions were made in regard to the correlation of the lymphocyte functions to the clinical stage. In the localized (disseminated) stages a good (bad) ability of the immune system to recover is suggested.

Growth characteristics and therapeutic response of transplantable colon tumors in animals.

The growth characteristics and the effect of clinically available chemotherapeutic agents on two transplantable colon tumor lines were studied. These are subcutaneously transplanted undifferentiated carcinoma AKATOL, originating from tumors "spontaneously" appearing after foetal colon implantation, and moderately differntiated carcinoma No. 173 obtained likewise with additional treatment by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Some basic kinetic parameters of tumor growth are determined. The tumors show a relatively slow growth, the median survival time of animals being approximately 50 and 38 days, respectively. The investigation of the sensitivity of tumor lines shows that they are sensitive to many standard antitumor drugs. In the case of AKATOL a high responsiveness to antibiotics and to a smaller degree to other groups agents was observed excluding sarcolysine, CCNU, alexan (cytosine arabinoside) and vinblastine. In the case of colon tumor No. 173 strong antitumor effect for CCNU, 5-fluorouracil, cyclophosphamide, methotrexate and vinblastine was observed. The possibilities to use these tumor systems for screening and evaluation of antitumor agents are discussed.

Some parameters of cell-mediated immunity in colon cancer patients.

16 colon cancer patients in the second clinical stage (according to the TNM classification), aged 34 to 71 years were studied before and 14 days after radical surgery. The in vitro cell-mediated immunity was evaluated using the rosette-forming test and blastogenic reactivity of blood lymphocytes to PHA. The percentage of total rosette-forming cells (T-cells) before and after surgery did not alter significantly (p less than 0.1). At the same time there was no significant difference between the number of rosette-forming cells in cancer patients compared to donors (p less than 0.1). Blastogenic reactivity of lymphocytes to PHA expressed as a stimulation index (S. I.) showed a significant decrease of that parameter in patients compared to donors (p less than 0.001). The S. I. was lower in patients 14 days after surgery than prior to treatment (p less than 0.01).

Spontaneous rosette formation in patients with oral cancer.

The percentage of "total" E-rosettes was studied in the peripheral blood of 38 untreated patients with squamous cell carcinoma of the oral cavity, performing the test at 4 degrees C and at 20 degrees C. At 4 degrees C the quantity of the E-rosettes was higher than at 20 degrees C. The mean value of E-rosettes was strongly reduced only in 17 of these patients with metastases in the regional lymph nodes when compared with a group of 40 normal individuals as well as with the group of remaining 21 patients with localized cancer (P less than 0.001), whatever the temperature of testing. The mean percentage of 20 degrees C E-rosettes was significantly higher in patients with localized disease than in the 22 normal donors (50.2 +/- 3.0% vs 41.8 +/- 2.0%, P less than 0.01) but in favour of 4 degrees C E-rosettes the difference was not significant (57.3 +/- 2.8% vs 54.2 +/- 2.9%). Thus there was a clear correlation between changes of the T cell level and the clinical stage of the disease.

Delayed hypersensitivity reactions in patients with breast cancer.

Fifty six patients with metastatic cancer of the breast (stage IV) were treated with Cyclophosphamide, 5-Fluorouracil and Cyclophosphamide + 5-Fluorouracil. Tests for delayed hypersensitivity to homologous tumor antigen before treatment were positive in 83.9% and negative in 16.1%. Response to DNCB was positive before treatment in 51.8% and negative in 48.2%. Following chemotherapy the skin reaction, to homologous tumor antigen remained positive, only in 12.6% and negative in 87.4%. The reaction of DNCB remained positive after treatment only in 17.8%. In the remaining 82.2% suppression of the reaction occurred. These data show that chemotherapy may suppress, to a certain excent, immune responses. It is established that among patients who have shown a positive reaction to homologous tumor antigen 55.3% of all cases have displayed objective response to the treatment, and among these with negative skin reactions objective responses were observed in 22.22% of all cases. In patients with positive DNCB reactions objective responses were observed in 79.3% and among the negative ones--in 37.4%.

[Kinetics of proliferation of a mouse tumor cell line originating in the fetal large intestine]. / Kinetika na proliferatsiia na kletuchna liniia ot mishi tumor, proizkhozhdasht ot fetalno debelo chervo

The authors examine the kinetics of cellular proliferation of the cellular line STS, originating from adenocarcinoma, obtained after "spontaneous" malignization of a fragment from fetal colon. The cells of STS grow as a single layer and reach exponential phase on the 48th hour, but stationary phase-on the 96th hour of the culture. Time for doubling the number of the cells TD at the exponential phase of growth is 12 hours. The mitotic index varies from 7% at the exponential phase to 1,3% at the stationary. Time of cellular cycle and its phases, estimated by the curves of the marked mitosis, shows the following values: TGi=5.3 hours, Ts=6 hours, TG2=0.5 hour, TM=1,2 hour, and TC=13 hours. The authors discuss the differences in the data of TC and TD.