Tolerance of half-body irradiation as systemic therapy for patients with locally advanced breast cancer.

BACKGROUND: Locally advanced breast cancer (LABC) is one of the main causes of cancer death among women in Bulgaria. In 1988, when this study started, there was still controversy about the role of chemotherapy in controlling systemic disease. There were encouraging results from the Radiation Therapy Oncology Group (RTOG) 82-06 study suggesting that half-body irradiation (HBI) should be used earlier in the disease course to prevent the development of metastases. There were many patients with LABC requiring treatment, but there was a problem with obtaining the drugs needed; they were expensive and not consistently available. PROCEDURE: Taking into account the medical contraindications to chemo-therapy treatment, its toxicity, and the possibility of chemoresistance, we initiated this study to look at the effects of HBI given as two fractions of 4 Gy to the upper and then lower parts of the body, after surgery and before local radiotherapy. RESULTS: The acute tolerance of this regimen in 36 patients with LABC was as good as it was in 4 additional LABC patients with M1 disease, and hematologic recovery was satisfactory. CONCLUSIONS: We conclude that systemic treatment with HBI is tolerable. It therefore may be a convenient and cost-effective treatment for LABC, although better treatments are still needed.

On the inhibitory activities of a new boron compound and ultrasound against the mouse ascites tumour.

The inhibitory effects of a new boron compound, dihydroxy (oxybiguanido) boron (III) hydrochloride monohydrate (HB), and ultrasound (US) of a frequency 25 kHz on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, weight of tumour-associated material, tumour cell count, serum alkaline phosphatase activity and the haematological parameters of the treated animals. 5-Fluorouracil (5-FU), a well-known anticancer agent, was used as positive control. While HB exhibited a very significant antitumour action, US alone produced a small but significant inhibitory effect. The combination of US with HB or 5-FU produced an extra antitumour action as compared to the actions of these chemicals used singly. The mechanisms of action of the new boron compound (HB) and US are discussed.

Difference in the effects of radioprotection between aerial and root parts of Lycium chinense.

Radiation protection from bone marrow death by consecutive injections of crude extracts from different parts of Lycium chinense (LC), root (LCR) and aerial part (LCA), before whole body X-irradiation was confirmed by tests with ICR strain mice. Both extracts were effective after intraperitoneal injection of a high dose, once a day, for seven consecutive days before irradiation. Based on the studies of endogenous hematopoietic spleen colony formation (CFUs), and the postirradiation behavior of hematograms and hematocrits, it was demonstrated that the LCR protects mice more effective when given in a dose of 500 mg/kg. Enhanced CFUs was found in the irradiation range of 4-8 Gy by various treatments. Recovery of leukocyte, erythrocyte and thrombocyte counts was significantly stimulated by the extract of LCR with 500 mg/kg administration. Stimulated recovery by the extract from the LCR was also observed in hematocrit. On the contrary, the extracts of both LCA and LCR did not markedly affect recovery of leukocyte, erythrocyte, thrombocyte counts and hematocrits by 250 mg/kg administration. It could be deduced that the uncertainly radioprotective action is induced by a possible process of enhanced regeneration of the hematopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hematopoietic stem cells under the suitable extract administration.

[A decrease in the level of erythrocytes with micronuclei under the influence of pyrimidine and thiazolidine derivatives in the blood of persons who came under radiation exposure as a result of the accident at the Siberian Chemical Combine]. / Snizhenie urovnia éritrotsitov s mikroiadrami pod vliianiem proizvodnykh pirimidina i tiazolidina v krovi liudei, popavshikh pod radiatsionnoe vozdeistvie v rezul'tate avarii na Sibirskom khimicheskom kombinate.

The authors have found that pentoxylum (pyrimidine derivative) and leucogenum (thyazolidine derivative) are capable or reducing the number of cells with micronuclei in the blood of people who suffered from the radiation accident at the radiochemical works of the Siberian chemical plant. The most effective decrease in the cells with micronuclei in adults was observed two weeks after treatment, while in children the same result was achieved with leucogenum on the third day.

Immune organs and haemopoietic system under modelling of the mission factors.

Literary and experimental data on the character of changes in immune organs and lymphoid tissue of respiratory system and digestive system in laboratory animals during the mission factors model area given. Inhibition of reproductive function in bone marrow, thymus and spleen under irradiation of gamma-rays and accelerated carbon ions, tensity of immune response in the lymphoid structures of larynx, trachea and bronchi under the influence of acetaldehyde vapors and decrease of lymphoid tissue square on histological series in spleen and small intestine with an increase of concentration of microbial bodies in the drinking water were estimated.

Biological effects of inhaled 144CeCl3 in beagle dogs.

The biological effects of 144Ce were studied in beagle dogs that were exposed to graded activity levels of 144CeCl3 via a single, brief inhalation exposure and observed for their life span. The long-term retained body burdens ranged from 0.06 to 13 MBq/kg with a median of 1.2 MBq/kg. After a short residence time in the lung, most of the 144Ce was translocated to liver and skeleton, where the 144Ce was retained with a half-time approaching the physical half-life of 144Ce, 284 days. Significant radiation doses were delivered to the lung, 28 Gy (median) and 2.5-370 Gy (range); liver, 68 Gy (median) and 6.1-250 Gy (range); and skeleton, 21 Gy (median) and 1.9-100 Gy (range). Lesions induced by the beta-particle radiation were noted in the lung, liver, skeleton, bone marrow, and oral and nasal mucosae closely associated with bone. Early deaths (within 2.5 years) were generally related to hematological dyscrasia, radiation pneumonitis, or hepatocellular degeneration and atrophy. Neoplasms that occurred relatively early, from 2.2-6.8 years after exposure, were noted in the liver, bone, bone marrow and oral mucosa closely associated with bone. Neoplasms that occurred later, beyond 7 years after exposure, were noted in the liver, lung and nasal mucosa closely associated with bone. Increased numbers of neoplasms were not found in two other organs that had relatively high radiation doses, namely the thyroid and kidney. Only one primary bone tumor was noted, but 11 tumors of bone-associated tissues (oral and nasal mucosae and bone marrow) were found. Radiation doses and effects in tissues adjacent to bone, especially those of epithelial or marrow origin, should be considered when determining risks from internally deposited bone-seeking radionuclides, such as 144Ce. The property of 144Ce in depositing on and remaining associated with bone surfaces for long times may be an important factor in the radiation dose to bone marrow and epithelium adjacent to bone.

Modulation of haemopoietic radiation response of mice by diclofenac in fractionated treatment.

The effects of diclofenac, an inhibitor of prostaglandin synthesis, were studied on the acute radiation syndrome elicited in mice by fractional irradiation. Several haematological parameters were evaluated in mice irradiated with 5x2 Gy and 3x, 4x, or 5x3 Gy (intervals between fractions 24 h) from a 60Co gamma-ray source. The animals were treated with diclofenac either before each fraction or only once before the last fraction. The survival of mice was recorded after the irradiation regimen of 5x3 Gy followed by a "top-up" dose of 3.5 Gy given 24 h after the last radiation fraction. Statistically significant enhancement of the endogenous spleen colony formation and of leukopoiesis was found in mice treated with diclofenac repeatedly, as compared with both saline-treated irradiated controls and animals administered a single diclofenac dose, if a sublethal total radiation dose had been accumulated. However, following accumulation of a lethal total radiation dose, slightly impaired survival was observed in mice given diclofenac. It follows from the results that diclofenac is a suitable drug for enhancing leukopoiesis impaired by sublethal fractionated irradiation. Nevertheless, undesirable side effects of this drug negatively influence the survival of experimental animals following a lethal accumulated radiation dose.

Time-dependent hematological changes in workers exposed to electromagnetic fields.

A World War II-era study, involving the effects of electromagnetic fields (EMFs) emanating from radars and high-frequency radios on the blood of exposed workers, was analyzed for evidence of the effect of time in the manifestation of changes in the hematological system. Statistically significant correlations between increasing white blood cell count and average daily exposure, months of exposure, and total duration of exposure to EMFs were found. Changes in cell count were within the normal range, and thus their relation to epidemiological studies linking EMFs and leukemia, if any, is unclear. Results suggest that the time of exposure may be an additional factor (along with field strength, and perhaps frequency) in ascertaining the safety of EMF exposure.

Persistent abnormalities in red cell parameters following treatment of lymphoma.

Patients who have recovered from malignant lymphoma are at an increased risk of secondary acute leukemia (AL), and overt AL is frequently preceded by a myelodysplastic syndrome. Although the statistical risk is significant, only a minority of the patients will be so affected. We have reviewed peripheral blood counts of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) treated in the Departments of Hematology at the Edith Wolfson and Chaim Sheba Medical Centers, Israel. Included were only those who went into a complete remission and remained lymphoma free for extended periods. There were 85 patients with HD and 36 with NHL. In both groups peripheral blood counts at diagnosis were within the normal range. A prolonged follow-up (> 4 y), during which no further treatment was given, revealed a sustained increment over time of MCV (delta MCV) both in HD and NHL. A persistent monocytosis in HD patients was also evident. delta MCV was larger in HD. The difference at the end of the follow-up period was as follows: 10.1 fl + 11.8 in HD vs 5.0 fl + 6.2 in NHL, (P < 0.001). In addition, a significant loss of the normal correlation between the MCV and levels of hemoglobin was seen at the last follow-up. The change in MCV was present in all treatment groups, its magnitude increasing from radiotherapy to chemotherapy to combined radio chemotherapy. This trend is in analogy to the risk of secondary AL which is lower in NHL vs HD. Furthermore, it is lowest post radiotherapy and highest when both treatment modalities are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic radiation-induced alteration in hematopoietic repair during preclinical phases of aplastic anemia and myeloproliferative disease: assessing unscheduled DNA synthesis responses.

Protracted, low-daily-dose gamma-ray exposure (3.8-7.5 cGy/day) segregates canines into separate survival- and pathology-based subgroups by the early elicitation of distinct, repair-mediated hemopathological response pathways. In this study, we verified the blood and marrow responses of two major subgroups prone to either aplastic anemia or myeloproliferative disease, along with two variants, and extended our analyses of hematopoietic repair to include studies of DNA repair in bone marrow blasts using an autoradiographically based unscheduled DNA synthesis (UDS) assay. The myeloproliferative disease-prone subgroup exhibited extended survival (> 200 days), related to partial, gradual restoration of blood leukocyte, platelet, and marrow progenitor levels following an initial phase of acute suppression. Marrow blasts taken during the restoration phase showed expanded and qualitatively modified UDS relative to marrow blasts of age-matched control animals. The amount of UDS per blast (signal strength) increased significantly, as did the number of UDS-positive cells and their sensitivities to high-dose UV induction and 1-beta-D-arabinofuranosylcytosine chemical inhibition. A nonevolving myeloproliferative disease-prone variant having prolonged survival (> 200 days) and restored blood cells and marrow progenitor levels also had marrow blasts with expanded UDS responses, but these were uniquely evoked by low (but not high) doses of UV inducer. The aplastic anemia-prone subgroup was characterized by short survival (< 200 days), progressive decline (without restoration) in all measured blood and marrow compartments, and largely nonsignificant changes in UDS responses of marrow blasts. A variant of this aplastic anemia-prone subgroup (with comparable short survival due to markedly ineffective hematopoiesis, but expressing select preleukemic features) exhibited reduced numbers (relative to age-matched controls) of highly responsive, UDS-positive marrow blasts (in terms of UDS signal strength and increased to sensitivity 1-beta-D-arabinofuranosylcytosine-induced UDS inhibition). From these observations we conclude that: (a) the UDS response of marrow blasts, a correlate of hematopoietic progenitorial repair, is altered differentially within selected subgroups of animals under chronic radiation exposure; and (b) the nature of altered UDS repair response patterns appears to be largely related to the preclinical status/predisposition of the individual animal and thus may provide prognostically useful information in the clinical monitoring of chronically irradiated individuals with minimal but evolving hematological disease.

[The biological effects of irradiation and hyperthermia]. / Biologicheskie éffekty oblucheniia i gipertermii.

Experimental data on the effects of radiation and hyperthermia on Chinchilla rabbits are presented. Multiple exposure to heat (40 degrees C, 20 min) between two radiation fractions was shown to influence favourably such haematological indexes as leukocyte and erythrocyte number and life-span of irradiated animals. Extra (to irradiation + heat) hyperthermia applied immediately before irradiation increased the radiation effect.

The effect of cold after whole-body irradiation of the mouse.

Mice were placed in a cold environment (4 degrees C) directly after whole-body irradiation. Those irradiated with a lethal dose showed higher lethality than mice irradiated with the same dose but placed in room temperature. The response was also altered after irradiation with a sublethal dose. At various periods after irradiation mice were injected with 125IUdR, the tissue uptake of which is an index of DNA synthesis. The result showed that cold treatment after irradiation caused slower cell renewal in the spleen and bone marrow, but that the thymus was only marginally affected. Furthermore, the concentrations of erythrocytes in the peripheral blood reached a lower level in the cold-treated group. Finally, the levels of the thyroid hormones T3 and T4 in the blood were measured and it was found that the T3/T4 ratio was higher in the cold-treated mice. It is suggested that during prolonged exposure to cold after irradiation the cell recovery in the haemopoietic system is exposed to hormonal action that induces significant alterations in the postirradiation cell kinetics.

[The biological effect of low-level radiation doses on the morphological composition of the peripheral blood in children]. / Biologicheskii éffekt malykh doz radiatsii na morfologicheskii sostav perifericheskoi krovi u detei.

Examination of 339 children at the age of 2 to 12 years, living in the caesium contaminated region (from 2 to 5 Ci/km2) has revealed that total radioactivity of their urine is, on the average, twice as high as that of children living in "pure" regions. Quantitative and qualitative changes were observed in the erythroid series, neutrophilic leukocytes, eosinophils and B-lymphocytes of the peripheral blood of children subjected to long-term low-level irradiation. It should be noted that the character and direction of these changes were a function of the children's age and the level of total radioactivity of their urine.

Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice.

Repeated injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to lethally irradiated mice increased the rate of animal survival. Dose modification factor was 1.20 when 4.5 micrograms/mouse of rhG-CSF was given daily for 14 days after whole body irradiation. Haematological examinations revealed that rhG-CSF increased the number of blood-circulating leukocytes, neutrophils, monocytes and erythrocytes, but not that of lymphocytes and thrombocytes. Spleen weight and number of endogenous spleen colonies were also increased by rhG-CSF treatment compared with the values for mice irradiated only.

Radioprotection of whole-body gamma-irradiation-induced alteration in some haematological parameters by cysteine, vitamin E and their combination in rats.

Radioprotective effect of cysteine, vitamin E and their combination on gamma-irradiation-induced alteration in some haematological parameters in male rats has been studied 24 and 48 hrs after whole-body gamma-irradiation at a dose level of 7.5 Gy. The results of this study reveal that gamma-irradiation caused a significant decrease in red blood cells (RBCs) count with insignificant change in hemoglobin level, 24 and 48 hrs postirradiation, gamma-irradiated rats showed as well a progressive decrease in their blood ATP, and serum-SH levels with a significant increase in blood glutathione (GSH) level. Administration of cysteine or vitamin E preceding gamma-radiation exposure gave a significant radioprotection to the above haematological parameters. However, combination of both agents afforded a better protection, so that most of the measured parameters were restored to the pre-irradiated values. Finally, the date demonstrate that the radioprotection provided by combined administration of vitamin E and cysteine is feasible and perhaps, even more efficient against radiation injury to RBCs. This will appreciate the usage of such combination in protecting the patient during radiotherapy.