The influence of postoperative cyclic chemotherapy for breast carcinoma on the blood lymphocyte population was examined in 21 recurrence-free women 4 to 6 years after completion of therapy. Chemotherapy consisted of combinations of chlorambucil, methotrexate and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil. It was observed that the lymphocyte numbers and mitogenic responses to PHA and in an MLC, known to be depressed during and shortly after treatment, had recovered to the levels of healthy age-matched women. NK activity, which is increased during the period of chemotherapy, still remained elevated.

Adult↗

PubMedDate not supplied

Stereotactic radiation therapy of intracranial lesions. Methodologic aspects.

A technique for stereotactic radiation therapy of cerebral tumours and arteriovenous malformations using a linear accelerator (6 MV photons) is proposed. Treatment relies on a fixation system that permits a precise use of the coordinates estimated at stereotactic angiography or stereotactic computed tomography. The field of treatment can be exactly outlined in the CT images during repeat examinations, thus facilitating the recognition of changes induced by radiation. The system also allows the extent of the arteriovenous malformation, as seen at angiography, to be accurately traced in the CT sections thus enabling evaluation of possible radiation damage to surrounding brain structures. The precision of the method as well as its hypothetical merits and disadvantages are discussed. The number of patients treated is still small and the follow-up time is too short in the majority of cases to allow definite conclusions. Examples of preliminary results are given.

Aged↗

PubMedDate not supplied

Monocyte release and plasma levels of interleukin-6 in patients irradiated for cancer.

Interleukin-6 (IL-6) release from purified blood monocytes was determined in patients with breast cancer or prostatic cancer before and after radiation treatment (Rx). Plasma levels of IL-6 and neopterin were also determined. Spontaneous IL-6 release in vitro was higher in breast than in prostatic cancer or in controls. Strong lipopolysaccharide (LPS)-induced cellular IL-6 release was detected in breast cancer and controls but was subnormal in prostatic cancer. Addition of indomethacin to cultures had no effect on IL-6 release. Rx generally increased levels of in vitro released IL-6 and raised LPS-stimulated IL-6 secretion in prostatic cancer to normal. Plasma levels of IL-6 were lower in breast than in prostatic cancer or controls. Rx resulted in a tendency towards raised levels in both patient groups suggestive of monocyte activation. In accordance with this, plasma levels of neopterin, which were normal before treatment, increased in prostatic cancer patients after Rx. Taken together, the results of this study indicate that monocyte release as well as plasma levels of IL-6 are affected by the malignant state as well as by radiation treatment. In view of the antiproliferative effects of IL-6, the findings may have bearing on the pathogenesis and treatment of malignant disease.

Adult↗

PubMedDate not supplied

Growth inhibition of human malignant glioma cells in vitro by agents which interfere with biosynthesis of eicosanoids.

In an attempt to find new methods for the treatment of malignant gliomas a number of tests have been performed to learn whether growth of such cells in vitro may be affected by agents which interfere with the biosynthesis of eicosanoids. It was observed that DNA-synthesis of short-term monolayer cultures could be blocked by compounds which inhibit cyclooxygenase and/or lipoxygenase dependent arachidonic acid metabolism. The strongest inhibitory activities were noted in serum-free culture medium using compounds interfering with the activity of lipoxygenases. One explanation of these results could be that the growth of human malignant gliomas is dependent on certain eicosanoids which may be synthesized by the malignant cells themselves.

Antineoplastic Agents↗

PubMedDate not supplied

Cytokine release from mononuclear cells in patients irradiated for breast cancer.

Mononuclear cells from blood of 19 breast cancer patients were cultured in vitro before and following postoperative radiation treatment. Interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1) were determined in supernatants from stimulated and unstimulated cultures with or without addition of indomethacin. The release of all three cytokines was uninhibited in tumour patients. Spontaneous IL-1 secretion was increased in patients compared to controls. Indomethacin enhanced IFN-gamma release and spontaneous and induced TNF-alpha secretion in all groups but stimulated IL-1 only in irradiated patients. In patients with a low tumour burden, ability to produce cytokines seems to be unchanged although increased spontaneous IL-1 secretion indicates macrophage activation. Cyclooxygenase inhibition in conjunction with irradiation might be tried as a therapeutic modality in patients with cancer.

Breast Neoplasms↗

PubMedDate not supplied

Antitumor activity of 2-mercaptoethanesulfonate (mesna) in vitro. Its potential use in the treatment of superficial bladder cancer.

2-Mercaptoethanesulfonate (mesna) is a nontoxic drug which upon intravenous and oral administration effectively prevents urothelial toxicity in cancer patients treated with oxazaphosphorines. Mesna is rapidly oxidized to dimesna in the blood. It is then taken up by kidney tubular cells in which it is reduced and excreted into the urine as mesna where it reacts with toxic metabolites. We have observed that mesna, but not dimesna, may inhibit growth of several human malignant cell lines in vitro. Some are extremely sensitive, whereas others are more or less resistant. It was found that 2/4 relatively resistant human bladder cancer cell lines turned sensitive upon repeated administrations of mesna and 5/5 cell lines appeared to be sensitive to mesna when grown in serum-free medium. The results seem to provide an explanation of the remarkable positive clinical effects of prolonged oral mesna treatment in patients with superficial bladder cancer.

Cell Line↗

PubMedDate not supplied

Possible role of acrolein in 4-hydroperoxycyclophosphamide-induced cell damage in vitro.

Unlike "conventional" oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide, a relatively new drug termed 4-hydroperoxy-CP (4-HC) degrades spontaneously in water yielding phosphoramide mustard considered to be the activated cytotoxic metabolite. During this degradation a toxic, volatile factor termed acrolein is also formed. In order to examine the possible role of this compound in 4-HC-induced inhibition of tumor cell growth in vitro, 8 different established human tumor cell lines were cultured in the presence of 4-HC or equimolar concentrations of acrolein. It was observed that the cell lines differed widely with respect to sensitivity to these compounds. However, each individual cell line exhibited virtually identical sensitivities to both 4-HC and acrolein. The observation that 2-mercaptoethansulfonate (mesna), which is highly reactive with acrolein but not with phosphoramide mustard, could markedly reduce the cytotoxic activity of 4-HC indicates that acrolein may play an important role in 4-HC induced cell damage in vitro.

Acrolein↗

PubMedDate not supplied

Changes of CD2 receptor density determined by electron microscopy on blood lymphocytes following radiation treatment for breast cancer.

Changes of relative CD2 receptor on lymphocytes were examined in 11 women following radiation treatment for breast cancer by electron microscopy using antibody-coated gold particles. Proportions of blood lymphocytes with a high density of CD2 receptors were reduced, whereas those with no or a low density of such receptors were increased after radiation treatment.

Antigens, CD↗

PubMedDate not supplied

Augmentation of spontaneous cytotoxicity of human lymphocytes by RU 41.740 is due to monocyte-derived factors distinct from interleukin 2, interferon alpha and gamma.

In vitro exposure of human blood lymphoid cells to RU 41.740 (Biostim), a glucoprotein extract of Klebsiella pneumoniae, augments spontaneous cytotoxicity of the lymphocytes. It was observed that the augmentation could be blocked by inhibitors of RNA- and protein-synthesis, but not by an inhibitor of DNA-synthesis. The increased cytotoxicity of Biostim-treated cells could not be explained by an increased proportion of lymphocytes binding to the target cells (K562). This indicates that Biostim acts by increasing the lytic activity of lymphocytes rather than by increasing the expression of target cell recognition structures. Further, it was shown that culture supernatants of Biostim-exposed monocytes, but not purified lymphocytes, contain factors that augment cytotoxicity of purified lymphocytes. This finding is in line with the previously reported monocyte-dependence of Biostim-induced augmentation of lymphocyte cytotoxicity. Interleukin-2 (IL-2) activity was not observed in supernatants of Biostim-exposed lymphoid cells and augmentation of lymphocyte cytotoxicity could not be inhibited by antibodies directed against interferon (IFN) alpha or gamma. This indicates that Biostim stimulates monocytes to liberate factors other than IL-2 or IFN which augment spontaneous cytotoxicity of lymphocytes.

Adjuvants, Immunologic↗

PubMedDate not supplied

Impact of adjuvant chemotherapy on spontaneous and poke week mitogen triggered immunoglobulin secretion of blood lymphocytes in operable breast cancer.

The objective of this investigation was to examine further the influence of postoperative adjuvant treatment with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) on the immune system in breast cancer patients and to explore whether such changes are related to prognosis. The 12 CMF courses which were given for a period of 1 year resulted in a progressive lymphopenia. The relative spontaneous secretions of IgA and IgG in vitro increased 4- and 2-fold respectively after the first 3 courses, whereas IgM secretion was unaffected. IgA and IgG secretions in PWM stimulated cultures were not changed, whereas there was a sharp decrease of IgM. The CMF-induced changes of Ig-secretions were similar in patients who developed recurrent disease during a 4-6 year follow-up (n = 11) and those who remained clinically disease-free (n = 14). The results are discussed in relation to the immunopotentiation which may occur following treatment with relatively low doses of chemotherapeutic agents.

Antibody Formation↗

PubMedDate not supplied

Augmentation of spontaneous cytotoxicity of human lymphocytes by RU 41.740, a glucoprotein extract of Klebsiella pneumoniae.

RU 41.740 (Biostim) is an extract of Klebsiella pneumoniae with immunomodulating properties. This substance was observed to augment spontaneous cytotoxicity of human blood lymphocytes provided that monocytes were present during Biostim treatment. Maximal augmentation was observed after 2 h of incubation. The F1 fraction, a glucoprotein which comprises approximately 20% of Biostim, and LPS from Klebsiella pneumoniae were also observed to augment spontaneous cytotoxicity of lymphocytes. Biostim treatment of K562 cells, which were used as target cells for killing, did not change their sensitivity to the lytic action of spontaneously cytotoxic cells.

Adjuvants, Immunologic↗

PubMedDate not supplied

Long-term effects on the immune system following local radiation therapy for breast cancer. III. Changes of spontaneous and lectin dependent cellular cytotoxicity.

Long-term effects of local radiotherapy (45 Gy) on the spontaneous and PHA-mediated cytotoxicity of the peripheral blood lymphocyte population was studied in disease-free breast cancer patients 5-6 and 10-11 years after treatment. The patients were all part of a randomized trial in which pre- or post-operative radiotherapy was evaluated against surgery only. PHA-mediated cytotoxicity for 51Cr-labelled chicken erythrocytes seemed to be somewhat increased in patients who were irradiated 5-6 years earlier (p less than 0.025). This increase was not detectable after a disease-free period of 10-11 years. No significant differences between the various treatment groups were observed for spontaneous cytotoxicity against Chang and K 562 cells. The proportion of Leu 7+ lymphocytes was significantly increased in patients who received radiation therapy 5-6 years earlier (p = 0.029) and there was a significant correlation between PHA-mediated cytotoxicity and proportion of Leu7+ cells.

Breast Neoplasms↗

PubMedDate not supplied

Mitogen stimulation of blood lymphocytes from patients with primary intracranial tumors. Correlation to histological tumor type.

Blood lymphocytes from 125 patients with primary intracranial tumors were examined for proliferative responses to PHA and PPD in parallel with lymphocytes from sex- and age-matched controls. The tests were performed prior to surgery, radiotherapy, or chemotherapy and a histological diagnosis was obtained in all cases. Depending on tumor type, patients were divided into the following four histological groups: astrocytomas, oligodendrogliomas, malignant gliomas (anaplastic astrocytomas and glioblastomas), and miscellaneous tumors (mainly meningiomas). PHA-responses were approximately 10% lower in patients with malignant gliomas not receiving corticosteroids in comparison to corresponding controls. No significant differences were observed in the other groups of patients if not being treated with steroids. PPD-responses were largely similar in all groups of non-steroid treated patients. In the corticosteroid treated groups PHA-responses were significantly reduced in patients with oligodendrogliomas and malignant gliomas, but this was not true of those with astrocytomas or those in the group with miscellaneous tumors. The mean steroid doses given at the time of testing were similar in all four patient groups. The treatment period was longest in malignant gliomas but reasonably similar in the other three groups. It is speculated that PHA-responses of lymphocytes from patients with oligodendrogliomas may exhibit an increased steroid sensitivity.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Capacity of sera from patients with primary intracranial tumors to support mitogen stimulation of blood lymphocytes. Correlation to histological tumor type.

Sera from 125 untreated patients with various histological types of primary intracranial tumors were examined for the capacity to support proliferative responses of lymphocytes to PHA and PPD in vitro. It was observed that sera obtained from groups of non-corticosteroid treated patients with astrocytomas, malignant gliomas (anaplastic astrocytomas and glioblastomas), and miscellaneous tumors (mainly meningiomas) did not differ significantly from sera obtained from a group of healthy subjects. However, sera from a group of patients with oligodendrogliomas exhibited a significantly reduced capacity to support PHA- and PPD-responses of both autologous and allogeneic lymphocytes. Corticosteroid treated patients seemed to have reduced serum activities regardless of histological tumor type. It is not known whether sera from patients with oligodendrogliomas contain increased amounts of factors which inhibit mitogen responses of lymphocytes, or whether they contain reduced amounts of factors which support stimulations in vitro.

Adrenal Cortex Hormones↗