Effects of humoral immunity and calreticulin overexpression on postoperative course in breast cancer.

The aim was to investigate whether the humoral immunity and overexpression of calreticulin in tumor tissue determined before surgery, correlate with incidence of metastases in breast cancer patients within two years after operation. Before operation, their humoral immunity and overexpression of caleticulin and Her-2/neu in tumor tissue were analyzed by immunohystochemistry. In 23 patients with metastases in regionally lymph nodes, seven had Her-2/neu overexpression.

Cyclooxygenase inhibitors in the chemoprevention of colorectal cancer.

The long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased risk for colorectal cancer. A major molecular target for cancer chemoprevention by these agents is the cyclooxygenase- 2 (COX-2) isoenzyme, although other molecular pathways can not be excluded. Data from both human and animal studies suggest that COX-2 is an early event of colorectal carcinogenesis.

The antitumor immune response in HER-2 positive, metastatic breast cancer patients.

The aim of this study was to determine the basis for anti-tumor immune reactivity observed in patients with human epidermal growth factor receptor-2 (HER-2) (3+) breast carcinoma using an in vitro model in which the role of the HER-2-specific monoclonal antibody Herceptin was also investigated. Patients with metastatic breast cancer who had their primary tumor resected were included in this study. Peripheral blood mononuclear cell (PBMC)-dependent cytotoxicity in the presence or absence of Herceptin were assessed using the survival of target breast adenocarcinoma MDA-MB-361 cells as a parameter in a (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test.

Effects of X-ray irradiation on the overexpression of HER-2/Erb-B2 on breast cancer cell lines.

Irradiation is the conventional treatment modality for cancer patients. However, besides its cytotoxic effects on malignant cells it might also affect the biology of surviving cells. Since overexpression of HER-2 receptors on malignant cells is a prerequisite for the therapeutic efficacy of Herceptin, it seems important to know whether previous irradiation changes their overexpression.

Antimelanoma immunity in vitiligo and melanoma patients.

Cutaneous melanoma and vitiligo are diseases etiology of which evolves around melanocytes. The nature of immunological disturbances associated with these diseases is not elucidated. The experiments performed in this work were aimed to determine antimelanoma immunotoxicity in patients with melanoma and patients with vitiligo.

Lyophilized whole human melanoma cells stimulate human PBMC proliferation and enhance suppressive action of PBMC toward survival of the same malignant cell line in vitro.

The goal of this work was to determine: a) do lyophilized human melanoma BG or Fem-X cells affect the proliferative capacity of normal human peripheral blood mononuclear cells (PBMC) and b) does the PBMC six-days preincubation in nutrient medium with FBS with, or without lyophilized human melanoma BG or Fem-x cells, affect their suppressive action on the survival of the same malignant cell line in vitro. In the aim to avoid any stimulating effect of FBS, other group of experiments were done in nutrient medium with human AB serum in order to determine: c) does the PBMC six-day-preincubation with lyophilized human melanoma BG or Fem-x cells affect their antiproliferative action on the corresponding malignant cell line in vitro and d) does the PBMC six-day preincubation with lyophilized normal PBMC, obtained from healthy volunteer (as a source of allogenous, but not of tumor antigens), affect their suppressive action on the survival of both melanoma BG and Fern-x cell lines in vitro. Results obtained in the presence of FBS in nutrient medium, showed that lyophilized BG cells induced a proliferation of the healthy PBMC, depending on the number of stimulating lyophilized cells.

Radio- and chemotherapy variably affect the general immunocompetence of lung cancer patients.

Objective: The evaluation of the effects of radiotherapy and chemotherapy on the immune status of lung cancer patients.

Experimental Design: Prospective nonrandomized study.

Setting: Hospitalized care.

The influence of surgery and anesthesia on lymphocyte functions in breast cancer patients: in vitro effects of indomethacin.

Surgical trauma and anesthesia may lead to the postoperative immunosuppression, the exact mechanism of which is still unresolved. Among various factors, the role of prostaglandine PGE2-mediated suppression was also proposed. We investigated the influence of surgery and two anesthetic regimes on lymphoproliferative response (LPR) to PHA and on NK cell activity (MTT) in breast cancer patients, as well as the effect of indomethacin, a PGE2 synthesis inhibitor, on these lymphocyte functions in vitro.

Effect of T-activin therapy on indomethacin modulation of lymphoproliferative response in vitro of melanoma patients.

Background: Several studies showed that PGE-mediated immunosuppression in cancer patients may be differentially affected by conventional oncologic therapy.

Methods: Since there is little evidence about the action of immunotherapy on this suppression mechanism, we investigated the effect of therapy with a thymic agent-T-activin, on in vitro modulation of lymphoproliferative response (LPR) by indomethacin.

Results: The results demonstrated that indomethacin added in vitro enhanced LPR in early stage melanoma patients before therapy.

Immunomodulation in vitro. The predictive value of in vitro testing of lung cancer patients' lymphocyte responsiveness to stimulation by Thymex L. A preliminary report.

Eleven lung cancer patients were selected for combined radio and immunotherapy with a thymic agent-Thymex L. The selection criteria included the pre-therapy testing of patients' immunocompetence and the responsiveness of their lymphocytes to the in vitro addition of Thymex L: only patients with a significant degree of immunodepression, whose depressed cellular immunity parameters (the number of total and active T cells and their mitogen-induced lymphoproliferative response) were significantly increased upon this agent's action in vitro, entered the study. The results of the pre-therapy in vitro stimulation correlated with those obtained after completion of radioimmunotherapy: the administration of Thymex L along with radiotherapy seances prevented iatrogenic deterioration of initial depression of general immunocompetence and enabled to overcome it to a certain degree.

Clinical and immunologic effects of T-activin therapy in early stage melanoma patients.

We investigated the clinical and immunological effects of T-activin therapy in early stage melanoma patients. Several immune parameters (the number of T cells-E-RFC and CD3+, their subsets-CD4+ and CD8+, the number of CD38+ and CD16+ cells, and mitogen-induced lymphoproliferative response-LPR) were analyzed in relation to the clinical course of the disease in patients treated by T-activin in addition to the surgery (n = 8), and in control patients treated by the surgery alone (n = 9). Immunological tests were performed before therapy and one month after the last (6th) cycle of T-activin, i.

[In vitro reactivity of lymphocytes after the addition of immunostimulatory drugs].

The in vitro immunomodulating, effects of two thymic extracts--Thymex L and Thymomodulin--on lymphocytes of lung cancer patients, were studied. The number of total and active T cell and PHA-induced lymphoproliferative response were evaluated before and after the addition of two different concentrations (5 mg/ml and 0.5 mg/ml) of these agents.

Continuous versus split-course irradiation for lung cancer. Immunological implications.

The therapeutical irradiation for lung cancer causes profound disturbances of host's general immunocompetence, the cellular immunodepression being the dominant finding. It is thought that split-course technique holds certain advantage over the continuous irradiation, since the former includes an interruption of 4 week duration, thus allowing the lymphopoietic system to recover to a certain degree. In this report, we compared the radiotherapy-due alterations of several parameters of cellular immunity (the number and function of total T cells, active T cells and the cells of monocyte/macrophage lineage), immediately after the completion of therapy in either continuously (n = 13) or split-course-irradiated (n = 12) lung cancer patients.

Immune reactive proteins in renal cell carcinoma patients treated by IFN alpha alone or in combination with vinblastine.

Immunoreactive proteins--serum immunoglobulins and immune complexes were evaluated in renal cell carcinoma (RCC) patients. The analyses were done after radical nephrectomy before, at the end, and six months after the therapy, with IFN alpha alone (in patients in Stage II) or IFN alpha in the combination with vinblastine (in patients in Stage III and IV of the disease). Data obtained before immuno- or immunochemotherapy show significant increase in IgG and IgA concentrations in RCC patients in all stages of the disease investigated--in comparison to controls, while circulating immune complexes were significantly elevated only in patients in the advanced Stages of the disease (III and IV).

[Immunologic reactivity in patients with breast carcinoma treated with interferon alpha].

We investigated the influence of the natural interferon alpha (IFN-alpha) on the nonspecific immune competence in the early stage of breast cancer. The IFN therapy, which started one month after surgery, lasted four months. Control group of patients received no therapy after surgical removal of the tumor.

[Immunomodulating effect of thymus protein fraction on disorders of general immunity in patients with lung carcinoma].

The parameters of both cellular and humoral non-specific immunity were evaluated in non-small lung cancer patients (n = 26) prior to therapy, in 13 of them after radiotherapy (45 Gy in 22 fractions) and in 13 patients after combined radio-and immunotherapy (Thymex L, 1800 mg in 12 injections á 150 mg i.m., three times a week).

Immunosuppressive and cytogenetic effects of pelvic irradiation on the peripheral lymphocytes of patients with cervical cancer. One year follow-up.

The circulating lymphocytes of patients treated for cervical cancer were examined by four independent manners: by evaluation of T-cell proportion in peripheral blood, proliferative response upon PHA stimulation, PHA-induced leukocyte migration inhibition, and by concomitant chromosome aberration frequency. The immediate and longer-term effects of pelvic irradiation on T lymphocytes were investigated in 19 patients prior to, during, and immediately after radiotherapy, and then at subsequent intervals of two, three and five months. Radiotherapy caused profound depression of already diminished T-cell number and their proliferative response; both parameters gradually recovered during post-treatment period, and achieved their pretreatment values at the end of follow-up.

Enhancement of phytohemagglutinin-induced lymphoproliferative response by indomethacin, Thymex L or their combination in lung cancer patients.

Several studies showed that thymic factors and prostaglandin synthesis inhibitors enhance in vitro lymphoproliferative response (LPR) to mitogens in cancer patients. In this study we investigated whether indomethacin and thymic extract (Thymex L), applied in combination, may in a synergistic pattern influence phytohemagglutinin-induced LPR in lung cancer patients. The results demonstrate that the use of the investigated agents enhances LPR to a similar level in hyporeactive patients before, as well as after, therapy.

The protective activity of Thymex L against radiotherapeutically-induced cellular immunodepression in lung cancer patients.

In order to prevent the radiotherapeutically-induced aggravation of initial immunodeficiency, a thymic preparation (Thymex L) was given to lung cancer patients simultaneously with irradiation. The parameters of both cellular and humoral nonspecific immunity were evaluated in two groups of patients: one was treated with radiotherapy only (60 Gy in 30 fractions); the other one received Thymex L (100 mg 3 times a week, total dose 1800 mg, i.m.

In vitro effect of indomethacin on mitogen-induced lymphoproliferative response in lung cancer patients.

There is some evidence that prostaglandin (PGE)-secreting cells may have a role in immunosuppression in cancer patients. In this work we investigated the effects of indomethacin--a PGE synthesis inhibitor, on PHA-induced lymphoproliferative response in vitro. Twenty patients with lung cancer before therapy were included in this study.

Lymphocyte reactivity in Imuran-treated guinea-pigs and in vitro effect of colchicine.

Imuran treatment significantly diminished macrophage migration inhibition in immunized guinea-pigs and the percentage of E-rosette forming cells in all treated animals. 10(-6) M colchicine in vitro significantly increased the percentage of E-rosette forming cells in Imuran-treated animals. The results suggest possible alteration of the lymphocyte receptors after treatment with Imuran.