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Biomedical subjects

H Blomgren

Publications and source records attributed to H Blomgren.

At least 73 records · Page 4Linked to original sources

Bestatin treatment enhances the recovery of radiation induced impairments of the immunological reactivity of the blood lymphocyte population in bladder cancer patients.

Bestatin, an immunostimulating substance of microbial origin, was examined for its capacity to augment immune responses of blood lymphocytes in bladder cancer patients having received a full course of local irradiation (64 Gy). Following irradiation the patients became lymphopenic and the lymphocytes exhibited impaired mitogenic responses to phytohemagglutinin (PHA) and purified protein derivative of tuberculin (PPD) and reduced poke weed mitogen induced secretion of immunoglobulins in vitro. Patients who were randomized to receive daily oral Bestatin treatment exhibited enhanced recoveries of PHA- and PPD-responses and enhanced recovery of the IgM secreting capacity compared to irradiated patients who did not receive Bestatin. Repopulation of the blood lymphocyte population, however, was not enhanced by Bestatin treatment. It is concluded that Bestatin treatment may enhance the recovery of radiation induced functional defects of the immune system in cancer patients.

Adjuvants, Immunologic↗

Blood lymphocyte counts with subset analysis in operable breast cancer. Relation to the extent of tumor disease and prognosis.

Blood lymphocyte counts and various lymphocyte subsets, as defined by rosette tests, were examined in breast cancer patients and correlated to the extent of tumor disease and prognosis. One hundred sixty-six patients tested before or shortly after surgery were included. It was observed that the frequency of E-rosette-forming lymphocytes correlated to the development of distant metastases (P = 0.007) and survival (P = 0.022). A high frequency of E-rosette-forming cells was associated with a poor prognosis. The well-known prognostic value of clinical tumor stage and axillary lymph node involvement was also confirmed. A possible relation between the tumor disease and other immune variables was indicated by the finding that the frequency of EAC-rosette-forming lymphocytes (mainly B-cells) was reduced in patients with relatively large primary tumors. This relation was most pronounced in patients without axillary node involvement (P less than 0.01). In addition, it was observed that the blood lymphocyte counts were significantly higher in patients with three or more tumor-involved axillary nodes than in those with zero to two (P less than 0.005). Our results seem to stand in contrast to the generally held view that low lymphocyte counts and a low proportion of E-rosette-forming cells in the blood are associated with a large tumor burden and a poor prognosis.

Adult↗

Cancer risks in patients with chronic lymphocytic thyroiditis.

The incidence of malignant tumors and leukemia was analyzed in 829 patients with chronic lymphocytic thyroiditis and in 829 individually age-matched and sex-matched patients with colloid goiter. Diagnoses were based on cytologic studies of specimens obtained by fine-needle aspiration biopsy. The patients were examined between 1959 and 1978 and were followed in the Swedish Cancer Register between 1959 and 1981. There was no increased risk for the total number of tumors in the thyroiditis group (53 observed vs. 52.7 expected) or in the colloid-goiter group (40 vs. 53.2, respectively; P not significant). There were six lung cancers in the thyroiditis group (2.9 expected, P not significant), and one in the group with colloid goiter. Patients with thyroiditis had an increased risk of myeloproliferative and lymphoproliferative neoplasms (12 observed vs. 3.0 expected, P less than 0.001). The risk of malignant thyroid lymphoma was greatly increased, with an estimated relative risk of 67 (4 observed vs. 0.06 expected, P less than 0.000001). There was no increased risk for any type of tumor among patients with colloid goiter.

Adult↗

Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers.

Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). Improved survival with Bestatin treatment following chemotherapy has been observed in patients with melanoma Stages 1b and II and in patients with acute nonlymphatic leukemia, where BCG also seems active, although possibly only in patient groups with less than 49% complete remissions.

Adjuvants, Immunologic↗

Hypocholesterolemia in cancer patients may be caused by elevated LDL receptor activities in malignant cells.

Several epidemiological studies indicate an inverse relation between plasma cholesterol and the occurrence of cancer. Since we in previous studies have found that certain malignant cell types have an elevated LDL receptor activity, the aim of the present study was to further explore the possibility that an elevated LDL consumption by tumor cells causes hypocholesterolemia. The plasma cholesterol concentrations in patients with acute leukemia were inversely correlated with the rate of receptor-mediated degradation of 125I-LDL by the leukemic cells. During chemotherapy, the total plasma and the LDL cholesterol levels increased concomitantly with the reduction in the leukemic cell count in a patient whose leukemic cells exhibited a high rate at receptor-mediated degradation of 125I-LDL. In certain patients with inoperable urinary bladder carcinoma, the plasma cholesterol concentration fell as the disease progressed. Studies in breast cancer patients indicate that the number of LDL receptors in the tumor tissue may have prognostic significance. The results are in agreement with the hypothesis that an elevated LDL receptor activity in malignant cells may lead to hypocholesterolemia.

Blood Donors↗

Long term effects on the immune system following local radiation therapy for breast cancer. I. Cellular composition of the peripheral blood lymphocyte population.

Local radiation therapy for breast cancer depletes the blood of various subsets of lymphocytes. Previous studies showed that the recovery is still incomplete at 30 months. To further elucidate the recovery we examined blood lymphocyte counts of 138 disease-free women and various lymphocyte subsets in 102 of these patients. These patients, 5-6 and 10-11 years earlier, had entered a clinical trial in which preoperative irradiation (45 Gy) was evaluated against postoperative irradiation (45 Gy) or surgery only. Patients who had undergone surgery only served as controls. Total lymphocyte counts of the irradiated patients were still significantly reduced 10-11 years after treatment. This reduction was mainly attributable to a subnormal level of T-cells as determined by the monoclonal antibody Leu-1 and the ability to form rosettes with sheep erythrocytes, whereas the number of non-T cells, expressing C'3 receptors, did not differ significantly from the controls. Within the T-cell population a subset with helper/inducer phenotypes, detected by Leu-3a antibodies, was significantly reduced even 10-11 years after irradiation. T-cells with suppressor/cytotoxic phenotypes, stainable with Leu-2a antibodies, however, had already recovered 5-6 years after irradiation. The duration of the radiation induced reductions of different lymphocyte subsets may be related to the physiological turn-over of the cells or a changed distribution of cells in the body.

Aged↗

Long-term effects on the immune system following local irradiation for breast cancer. Pokeweed mitogen induced immunoglobulin secretion by blood lymphocytes and serum immunoglobulin levels.

Previous studies have shown that the PWM driven immunoglobulin (Ig) secretion by blood lymphocytes in vitro is reduced shortly after local radiation therapy for breast cancer. In this investigation we have examined the long-term effects of radiation therapy (45 Gy) on this lymphocyte function. A total of 111 disease-free patients treated for operable breast cancer 5-6 and 10-11 years earlier were examined. The Ig classes studied were IgM, IgA and IgG. All patients belonged to a clinical trial where the effect of pre- or post-operative local radiation therapy was evaluated against surgery only. Significant reductions of the amount of spontaneously released IgM in vitro were observed among irradiated patients as compared to the unirradiated 5-6 and 10-11 years after treatment. Such a difference was not observed for IgA and IgG. The PWM induced Ig secretions did not differ significantly between the three patient groups. The long standing reduction of the spontaneous release of IgM by blood lymphocytes in vitro probably lacks clinical significance since the serum levels of this Ig class, as well as IgA and IgG, were similar in irradiated and unirradiated patients.

Aged↗

Antiestrogen effects on human blood lymphocyte subpopulations in vitro.

Human blood lymphocytes were incubated for 24 hr in medium containing various therapeutic concentrations of the antiestrogenic drug Tamoxifen. This treatment resulted in a diminished expression of C'3-receptors on the cells as detected by a rosette technique (EAC-rosettes). The expression of membrane receptors for sheep red blood cells (SRBC) was not changed under the experimental conditions used.

Adult↗

Treatment of patients with disseminated colorectal cancer with recombinant human alpha 2-interferon. Studies on the immune system.

The influence of recombinant human alpha 2-interferon (alpha 2-IFN) therapy on various aspects of the immune system was studied in 18 patients with disseminated colorectal cancer. The IFN was given as continuous (20 X 10(6) units/m2 three times weekly) or intermittent (50 X 10(6) units/m2 daily for 5 consecutive days every 4 weeks) treatment. Natural killer (NK) cell activity increased during continuous treatment and in the patients receiving repeated cycles of IFN, all cycles seemed to be associated with an elevation of NK activity. Prior to treatment, addition of IFN to the assay in vitro induced an enhancement of NK activity, whereas during treatment, IFN in vitro did not cause any further enhancement of NK activity. The proportions of total T cells, suppressor T cells and helper T cells, as measured by Leu 1, Leu 2a and Leu 3a monoclonal antibodies, were not altered to any major extent during treatment. This was found to be the case also for the number of cells detected by monoclonal antibodies against NK cells (Leu 7). The phagocytic activity of granulocytes was not altered during IFN therapy, whereas the capacity of these cells to reduce nitroblue tetrazolium (NBT) increased after the first injection of IFN. The in vivo influence of high doses of highly purified recombinant alpha 2-IFN on NK cells and granulocytes seems to be similar to that of partially purified natural IFN-alpha.

Adenocarcinoma↗

Changes of blood T cell subsets in patients receiving postoperative adjuvant chemotherapy for breast cancer.

The number of T helper (Th) and T suppressor (Ts) cells, as defined by monoclonal antibodies, of the blood lymphocyte population was examined in breast cancer patients receiving postoperative cyclic therapy with cyclophosphamide, methotrexate and 5-fluorouracil. The total number of lymphocytes was reduced to approximately 50% at the end of the 17-month period of chemotherapy. Identification of Th and Ts subsets with the aid of Leu-3a and Leu-2a antibodies revealed that the former was reduced to a higher relative extent than the latter, thus reducing the Th/Ts ratio highly significantly during the entire treatment period. A reduced ratio was also observed in a group of patients having completed their treatment 2-3 yr earlier.

Adult↗

Possible role of prostaglandin producing monocytes in the depression of mitogenic responses of blood lymphocytes following radiation therapy.

Previous studies have shown that the depression of mitogenic responses of cultured blood lymphocytes following radiation therapy can largely be explained by immunosuppressive cells. In this investigation we have shown that the addition of silica, a monocyte toxic agent, to the cultures enhance the PHA- and PPD-responses of the cells at completion of irradiation. Such an effect, however, was not noted before radiation treatment was started. Similar results were obtained by adding indomethacin, an inhibitor of prostaglandin synthesis, to the cultures. The results thus indicate that immunosuppressive monocytes which mediate their activity by prostaglandins are involved in the reductions of mitogen responses of blood lymphocytes following irradiation.

Adult↗

High dose rDNA human alpha 2 interferon therapy in patients with advanced colorectal adenocarcinoma: a phase II study.

Eighteen patients with advanced and inoperable colorectal adenocarcinomas were treated with high doses of alpha 2 Interferon (Schering-Plough Corporation). The patients were randomized to receive either subcutaneous injections of 20 X 10(6) I.U./m2 three times weekly for 3 months, or pulsed treatments of 50 X 10(6) I.U./m2 daily, given intravenously, for 5 consecutive days every 4 weeks. No objective tumour regression was seen in any patient. The side effects were considerable.

Adenocarcinoma↗

Interferon-alpha treatment of a patient with acute lymphoblastic leukaemia and Down's syndrome. Effects on natural killer cell activity and mitogen responsiveness.

A 32-year-old female with Down's syndrome and common ALL was treated with human leucocyte interferon-alpha (IFN-alpha) at a dose of 3 X 10(6) units i.m. daily. Side-effects consisted of slight tenderness and localized haematomas at the sites of injection. During treatment the number of leukaemic cells decreased in the peripheral blood. The proportion of blast cells in the bone marrow decreased only slightly, but a large fraction of them became vacuolized. After the initial response the disease progressed and IFN was withdrawn after treatment for 67 d. Prior to initiation of IFN treatment the natural killer activity of the patient's lymphocytes, as well as the response of these cells to mitogenic stimuli, was low. During IFN therapy these functions increased. Following the withdrawal of IFN therapy the patient received vincristine/prednisone treatment and a complete remission was achieved after 5 weeks. She is still in remission and on maintenance therapy 24 months after initiation of treatment.

Adult↗

Immunological and haematological monitoring in bladder cancer patients receiving adjuvant bestatin treatment following radiation therapy. A prospective randomized trial.

In a prospective randomized trial the clinical value of Bestatin, a low molecular weight immunomodulator, is being examined in patients having completed a full course of local radiation therapy for bladder cancer. At termination of irradiation (64 Gy in eight weeks) the patients are divided into two treatment arms: (i) 10 mg of Bestatin orally three times daily without breaks for at least one year and (ii) no further adjuvant treatment. Routine haematological monitoring of 68 patients for a period of up to two years did not reveal any differences between the two groups. Studies on the blood lymphocyte population, however, showed a significantly elevated frequency of cells forming rosettes with sheep erythrocytes after one month of Bestatin treatment. Upon continuation of treatment, however, this value declined and reached the level of the control patients at three months. The frequencies of lymphocytes with Fc-receptors for IgG or complement were unaffected by Bestatin. Spontaneous cytotoxicity against Chang cells appeared to be increased during the first three months of Bestatin treatment in those patients who survived for more than 18 months. No increase was observed in patients who died earlier. Although the above data seem to indicate that Bestatin should be administered at higher doses and intermittently instead of continuously, our preliminary results on disease-free survival in a limited patient material seem to be in favour of the Bestatin treated patients.

Adjuvants, Immunologic↗

Effect of estrogens on human blood lymphocyte subpopulations in vitro.

Human blood lymphocytes were incubated for 24 hr in medium containing different physiological concentrations of 17 beta-estradiol and estrone. Both hormones caused a diminished expression of C'3 receptors on the cells, as detected by a rosette assay (EAC-rosettes). The expression of membrane receptors for sheep red blood cells (SRBC) was impaired by estrone, but not by 17 beta-estradiol.

Adult↗

Prognostic value of various immunological tests in breast cancer patients treated with adjuvant postoperative chemotherapy.

Eighty-three patients, operated for carcinoma of the breast, received adjuvant therapy with chlorambucil, methotrexate and 5-fluorouracil or cyclophosphamide, methotrexate and 5-flourouracil. This group was subjected to a study exploring prognostic value, as defined by disease-free survival, of some immune variables. These included numbers of blood lymphocytes expressing membrane receptors for sheep erythrocytes (mainly T-cells), receptors for C'3 (mainly B-cells) and proliferative responses of the cells to phytohemagglutinin, purified protein derivative of tuberculin and in a mixed lymphocyte culture. Follow-up time was 30-71 months after start of adjuvant therapy. None of these variables showed any significant relation to prognosis in the present patient material. In addition, there was no detectable relation between numbers of eosinophils in the blood and disease-free survival. The well-known importance of tumor size and/or involvement of axillary nodes was, however, confirmed.

Adult↗