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PubMed1990

Increased pulmonary toxicity with bleomycin and cisplatin chemotherapy combinations.

Combination chemotherapy that included bleomycin and cisplatin was administered to 45 evaluable patients (30 with cervix carcinoma and 15 with germ cell tumors). Bleomycin was given, following cisplatin infusion, either by intravenous continuous infusion over 72 h (germ cell tumor patients) or intramuscularly every 12 h for 4 days (cervix carcinoma patients). Total bleomycin doses ranged from 156 to 360 U. Nine patients with normal renal function and no previous pulmonary disease prior to chemotherapy developed serious pulmonary toxicity. Six patients died from irreversible respiratory failure. Postmortem lung studies were performed in all six patients and revealed findings compatible with bleomycin-induced lung toxicity. Renal tubular damage was found in four kidneys available for examination. Five (71.5%) of the seven patients whose serum creatinine increased after chemotherapy was initiated developed lung injury, whereas 10.5% of those without change in the serum creatinine level presented this complication (p = 0.001). Renal damage, following cisplatin administration, with subsequent accumulation of bleomycin was the likely cause of the high lung toxicity. Extreme caution is recommended in the administration of combined bleomycin-cisplatin chemotherapy. Whenever possible, bleomycin should precede cisplatin infusion to minimize the risk of lung toxicity.

Adult↗
PubMed1988

Bleomycin causes alveolar macrophages from cigarette smokers to release hydrogen peroxide.

Alveolar macrophages (AM) were retrieved by bronchoalveolar lavage from 20 patients. Following AM purification by glass adherence, the effect of bleomycin on hydrogen peroxide and lactic dehydrogenase release was assessed by colorimetric methods. All AM from nine nonsmokers had no detectable spontaneous release of hydrogen peroxide. The AM did not release hydrogen peroxide when stimulated with bleomycin (25 mU/mL). AM from all eleven smokers spontaneously released hydrogen peroxide (36 +/- 5.3 nm/10(6) AM, mean +/- SEM). AM from eight of the eleven smokers released more hydrogen peroxide when incubated with bleomycin (smokers 55 +/- 6.8 nm/10(6) AM, p less than 0.05). There was no difference in the amount of lactic dehydrogenase released by AM spontaneously or when incubated with bleomycin at 25 mU/mL, suggesting that this dose of bleomycin was not directly toxic to the AM. Results from this study further support the premise that bleomycin pulmonary toxicity may result from the generation of reactive oxygen metabolites and that cigarette smoking may predispose to bleomycin pulmonary toxicity.

Bleomycin↗
PubMed2001

Sequence-dependent cytotoxicity of combination chemotherapy using paclitaxel, carboplatin and bleomycin in human lung and ovarian cancer.

Combination chemotherapy for non-small cell lung cancer (NSCLC) and ovarian cancer typically consists of a regimen of a taxane such as paclitaxel and a platinum-containing agent. Bleomycin, which halts cell cycle progression at G2 phase, is an agent which might thereby increase taxane cytotoxicity. The goal of this study was to evaluate the effect of different paclitaxel-platinum or paclitaxel-bleomycin schedules on cytotoxicity in human NSCLC and ovarian cancer cells. The simultaneous combination of paclitaxel and carboplatin exhibited simple additivity in vitro, while sequential exposure studies indicated that carboplatin followed by paclitaxel produced greater than additive cytotoxicity using the isobologram analysis of combinatorial effects. In contrast, the simultaneous combination of paclitaxel and bleomycin consistently exhibited greater than additive effects indicating a potentially synergistic combination. Sequential exposure studies of bleomycin followed by paclitaxel produced similar synergistic findings. Experiments in SCID mice evaluating the combinations of paclitaxel and bleomycin supported the in vitro results, as significantly enhanced A549 lung tumor growth inhibition was observed when paclitaxel was administered 1 h after bleomycin. The synergistic activity shown by the combination of bleomycin and paclitaxel indicates a potentially beneficial novel combination for treatment of NSCLC and ovarian cancer.

Animals↗
PubMed1977

Effects of bleomycin on the epidermal content of growth-regulatory substances (chalones).

Hairless male mice were given 2 mg Bleomycin i.p. on two successive days. At different time intervals from 1 to 10 days after the last Bleomycin injection, groups of animals were killed and water extracts of hemogenized skin were made. These extracts, supposed to contain the epidermal G1 and G2 chalones, were injected into female hairless mice, and their growth inhibitory potency determined by two methods. 5 mg of lyophilized crude skin extract were injected i.p. together with Colcemid, and the animals killed 4 hr later. The number of Colcemid-arrested mitoses was determined, and was considered to be a measure of the G2 inhibitor present in the skin extracts. 10 mg of the same extracts were injected i.p., and these animals also got 3H-TdR i.p. 12 hr later, and were killed after a subsequent 30 min. The epidermal LI was determined, and was considered to be a measure of the epidermal G1 factor in the skin extracts. The results obtained were compared to the effect of Bleomycin alone and to the effects of skin extracts from non-Bleomycin-treated animals. The results show that Bleomycin provoked slight alterations in the growth-inhibitory potency of the G1 chalone, whereas significant effects were seen in the G2 chalone, There was an increased amount of growth-inhibiting factors on days 2 and 3, and on days 8-10. The results are discussed and it is concluded that the most probable hypothesis is that Bleomycin, in addition to its known inhibition by accumulation of cells with high growth inhibitory potency. An initial, additional direct effect of Bleomycin on the chalone system cammot be excluded.

Animals↗
PubMed2005

Plasminogen activator inhibitor-1 is elevated, but not essential, in the development of bleomycin-induced murine scleroderma.

Accumulative data have demonstrated that plasminogen activator inhibitor-1 (PAI-1) plays an important role in the extracellular matrix metabolism; however, the involvement of PAI-1 in scleroderma has not been fully elucidated. In this study, we investigated the role of PAI-1 in bleomycin-induced murine scleroderma. 100 microg of bleomycin was injected subcutaneously to the back skin of C3H/HeJ mice on alternate day for 4 weeks. Histopathological findings revealed that PAI-1 was positive in macrophage-like cells and fibroblastic cells in the dermis, in parallel with the induction of dermal sclerosis. PAI-1 mRNA expression in the whole skin was up-regulated at 1 and 4 weeks. The production of active PAI-1 protein in the lesional skin was significantly increased 3 and 4 weeks after bleomycin treatment. Next, we examined whether dermal sclerosis is induced by bleomycin in PAI-1-deficient (PAI-1-/-) mice. 10 microg of bleomycin was subcutaneously injected to PAI-1-/- and wild type (WT) mice 5 days per week for 4 weeks. Histological examination revealed that dermal sclerosis was similarly induced even in PAI-1-/- as well as WT mice. Dermal thickness and collagen contents in the skin were significantly increased by bleomycin injection in both PAI-1-/- and WT mice, and the rate of increase was similar. These data suggest that PAI-1 plays an important role, possibly via TGF-beta pathway activation. However, the fact that PAI-1 deficiency did not ameliorate skin sclerosis suggest that PAI-1 is not the essential factor in the development of bleomycin-induced scleroderma, and more complex biochemical effects other than PA/plasmin system are greatly suspected.

Animals↗
PubMed1981

Distance geometry analysis of the N.M.R. evidence on the solution conformation of bleomycin.

Conformational constraints derived from n.m.r. experiments, X-ray data and the known stereochemistry have been used to investigate by the distance geometry method the range of allowed solution conformations for Cu(II):P-3A (a biosynthetic precursor of bleomycin), Fe(II):bleomycin:carbon monoxide, and Zn(II):bleomycin. The experimental data have been found to be self-consistent and lead to the following observations. 1) Designation of the ligands and the dihedral angles available from vicinal coupling constants are not sufficient to define uniquely the geometry around the metal. 2) When only five bleomycin ligands are invoked (e.g. Cu(II):P-3A or Fe(II):bleomycin:carbon monoxide) there is considerable freedom in the allowed coordination scheme around the metal, but some regions of the molecule have well determined conformation. 3) Introduction of a sixth bleomycin ligand, as in Zn(II):bleomycin, considerably constrains the conformational freedom of the groups coordinated to the zinc. The utility of the distance geometry approach for analysis of data and design of experiments is discussed.

Bleomycin↗
PubMed1997

Production of bleomycin N-acetyltransferase in Escherichia coli and Streptomyces verticillus.

Bleomycin-producing Streptomyces verticillus ATCC 15003 has two bleomycin resistance genes, designated blmA and blmB. Bleomycin N-acetyltransferase, encoded by blmB, was overproduced in Escherichia coli as a protein fused to the maltose-binding protein. The protein (fBAT), purified to homogeneity after digestion of the fusion product with blood coagulation factor Xa protease, had an additional 6 N-terminal amino acid residues, but retained its bleomycin-acetylating activity, as did the entire fusion protein. The K(m) and Vmax values of purified fBAT for the substrate bleomycin were 13.0 microM and 3.4 nmol [corrected] min-1 ml-1, respectively. The optimal pH for the acetylating activity was 6.0 in 10 mM phosphate buffer. The molecular mass and pI value of fBAT were estimated by polyacrylamide gel electrophoresis to be about 34500 and 6.13, respectively. An anti-fBAT monoclonal antibody was generated and used to show that bleomycin N-acetyltransferase is expressed simultaneously with bleomycin production in S. verticillus.

Acetyltransferases↗
PubMed2006

Preventive effect of melatonin on bleomycin-induced lung fibrosis in rats.

Oxidative stress has an important role in the pathogenesis of idiopathic pulmonary fibrosis. Melatonin has direct and indirect free radical-detoxifying activity. The present study investigated whether melatonin treatment attenuates bleomycin-induced lung fibrosis in rats. A group of rats was given one dose of bleomycin while the control animals were given saline. The first dose of melatonin (4 mg/kg/day) was given 2 days before the bleomycin injection. At day 14, fibrotic changes were evaluated using Aschoft's criteria and lung hydroxyproline content. Bleomycin produced a 2.7-fold rise in the fibrosis score that was decreased 65% by melatonin (P < 0.05) and a 1.4-fold increase in hydroxyproline content which was completely prevented by melatonin. Protein carbonyl and thiobarbituric acid reactive substances levels, which were significantly elevated in the bleomycin treated rats, were significantly attenuated by melatonin. Bleomycin administration significantly reduced the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissue. The reduction in CAT activity was prevented by melatonin but SOD and GSH-Px were not influenced. These results revealed that melatonin may prevent the development of bleomycin-induced lung fibrosis via the repression of protein and lipid peroxidation.

Animals↗
PubMed1982

Modulation of bleomycin cytotoxicity.

Lethal effects of a 75-microgram/ml concentration (approximately 5 X 10-5 M) of bleomycin on stationary-phase haploid or diploid cells of the eucaryote Saccharomyces cerevisiae were negated in the presence of 0.05 M phosphate buffer (pH 7). High cell densities (2 X 10(8) cells per ml) further inhibited killing. Multiphasic survival curves resulting after treatments in deionized water (pH 6.7) suggested the presence of cells with differing susceptibilities either at the start of treatment periods or as a result of resistance which developed during exposure to antibiotic. To identify a delayed effect, prolonged lethal consequences of the action of bleomycin were investigated under liquid-holding conditions. Survival of untreated early-stationary-phase yeast cells was not significantly affected by incubation without antibiotic for 6 or 36 h in non-nutrient buffer or water. However, increased killing resulted after bleomycin-treated cells were incubated in the absence of bleomycin or buffer. Moreover, cells which had never been exposed to the antibiotic lost considerable colony-forming ability as a result of incubation with bleomycin-treated cells, indicating the efflux of bleomycin or a reaction product. The findings have implications for both experimental cell studies and cancer therapy, as well as for the chemical mechanisms by which a metal bleomycin complex could cause killing.

Bleomycin↗
PubMed2002

P-selectin upregulation in bleomycin induced lung injury in rats: effect of N-acetyl-L-cysteine.

BACKGROUND: A number of adhesion molecules are involved in the process of neutrophil infiltration into the lung. P-selectin is one of these neutrophil-endothelial cell adhesion molecules. A study was undertaken to examine the involvement of P-selectin in the development of bleomycin induced inflammation and the ability of N-acetyl-L-cysteine to reduce the potential expression of this selectin in rats. METHODS: N-acetyl-L-cysteine (3 mmol/kg po) was administered daily for seven days prior to bleomycin administration (2.5 U/kg). The kinetics of P-selectin expression and the effect of N-acetyl-L-cysteine after bleomycin treatment were measured using radiolabelled antibodies. P-selectin localisation was evaluated by immunohistochemistry and neutrophil infiltration was assessed by myeloperoxidase activity. RESULTS: Bleomycin administration resulted in an upregulation of P-selectin at 1 hour, returning to baseline at 3 hours. Myeloperoxidase activity showed a significant increase at 6 hours after bleomycin administration that lasted for 3 days. N-acetyl-L-cysteine treatment completely prevented these increases. CONCLUSION: Upregulation of P-selectin in the lung is associated with neutrophil recruitment in response to bleomycin. The beneficial effect of N-acetyl-L-cysteine on bleomycin induced lung injury may be explained in part by the prevention of neutrophil recruitment in the inflammatory stage of the disease.

Acetylcysteine↗
PubMed2003

Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats.

BACKGROUND: Corticosteroids are routinely used in patients with pulmonary fibrosis. The timing for initiation of treatment is likely to be crucial for corticosteroids to exert an antifibrotic effect. Experimental studies in animals have examined the effect of corticosteroid treatment starting before or at the time of lung injury. However, this is not representative of the human condition as treatment only begins after disease has been established. We examined the effect of a short course corticosteroid treatment starting 3 days after bleomycin induced lung injury on the development of pulmonary fibrosis. METHODS: Bleomycin (1.5 mg/kg) was instilled intratracheally into rats to induce pulmonary fibrosis. The effect of a 3-day course of dexamethasone (0.5 mg/kg) initiated 3 days after bleomycin induced lung injury on cell proliferation and collagen deposition was examined by analysing bronchoalveolar lavage (BAL) fluid and lung tissue. RESULTS: Treating bleomycin exposed animals after injury with dexamethasone for 3 days inhibited lung collagen deposition compared with animals exposed to bleomycin without dexamethasone treatment (15.2 (2.2) mg collagen/lung v 22.5 (2.1) mg/lung; p<0.05). Dexamethasone treatment reduced pulmonary parenchymal cell proliferation in bleomycin exposed rats but did not influence BAL fluid mitogenic activity for lung fibroblasts or alter the BAL fluid levels of the fibrogenic mediators transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin. CONCLUSIONS: A 3 day course of dexamethasone treatment initiated 3 days after bleomycin induced lung injury reduces lung cell proliferation and collagen deposition by mechanisms other than through reduction of transforming growth factor-beta(1), platelet derived growth factor-AB, and thrombin levels in BAL fluid. We propose that an early short course treatment with dexamethasone may be useful in inhibiting pulmonary fibrosis.

Animals↗
PubMed1983

57Co-bleomycin and 67Ga-citrate in detecting and staging lung cancer.

In the investigation of suspected lung cancer bleomycin labelled with cobalt-57 and gallium-67 labelled with citrate are currently used to detect the primary tumour and to establish the presence of metastases in the lung hilum and mediastinum. A comparative study of these radio-pharmaceuticals was performed in 63 patients with proved lung cancer. 57Co-bleomycin showed the primary tumour in 58 patients (92%) and 67 Ga-citrate in 34 (54%) (p less than 0.01). The average tumour-to-lung ratio was 3.4 with 57Co-bleomycin and 1.5 with 67Ga-citrate. Proved metastases in the hilum or the mediastinum were visualised with 57Co-bleomycin scintigraphy in 16 out of 18 patients (89%) and with 67 Ga-citrate scintigraphy in only eight (45%) (p less than 0.01). These results indicate that 57Co-bleomycin scintigraphy is more suitable for detecting and staging lung cancer than is 67Ga-citrate. 57Co-bleomycin is valuable in the detection of peripheral lesions, in which a pathological diagnosis is difficult to achieve, since a positive scintigram indicates malignancy. When 57Co-bleomycin scintigraphy suggests hilar or mediastinal metastases mediastinoscopy should be carried out; but when no metastases are apparent it is reasonable to proceed directly to thoracotomy without mediastinoscopy.

Adult↗
PubMed1989

Augmentation of bleomycin-induced DNA damage in intact cells.

Bleomycin, an important cause of pulmonary fibrosis, is known to produce DNA damage. The mechanism for this damage in vitro is related to free radical production by a bleomycin and iron complex. To determine whether bleomycin causes damage to DNA in vivo by a similar mechanism, we used a viral minichromosome that is replicated in cultured cells. Bleomycin causes dose-dependent damage to intracellular DNA, and this damage is augmented by Fe2+ but not Fe3+. The augmentation of the bleomycin-induced DNA damage caused by Fe2+ is also dose dependent in that increasing DNA damage occurs with increasing amounts of Fe2+. These studies demonstrate that bleomycin causes damage to DNA in vivo and suggest that bleomycin must rely on Fe2+ to donate an electron for oxygen radical-induced DNA strand scission.

Animals↗
PubMed2005

Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice.

The balance between prostacyclin and thromboxane A2 (TXA2) plays an important role in pulmonary homeostasis. However, little information is available regarding the therapeutic potency of these prostanoids for pulmonary fibrosis. We have recently developed ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Thus we investigated whether repeated administration of ONO-1301 attenuates bleomycin-induced pulmonary fibrosis in mice. After intratracheal injection of bleomycin or saline, mice were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle. Bronchoalveolar lavage (BAL) and histological analyses were performed at 3, 7, and 14 days after bleomycin injection. In vitro studies using mouse lung fibroblasts were also performed. ONO-1301 significantly attenuated the development of bleomycin-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. ONO-1301 significantly reduced total cell count, neutrophil count, and total protein level in BAL fluid in association with a marked reduction of TXB2. A single administration of ONO-1301 significantly increased plasma cAMP level for >2 h. In vitro, ONO-1301 and a cAMP analog dose-dependently reduced cell proliferation in mouse lung fibroblasts. The reduction in cell proliferation by ONO-1301 was attenuated by a protein kinase A (PKA) inhibitor. Furthermore, bleomycin mice treated with ONO-1301 had a significantly higher survival rate than those given vehicle. These results suggest that repeated administration of ONO-1301 attenuates the development of bleomycin-induced pulmonary fibrosis and improves survival in bleomycin mice, at least in part by inhibition of TXA2 synthesis and activation of the cAMP/PKA pathway.

Animals↗
PubMed2004

Early response to bleomycin is characterized by different cytokine and cytokine receptor profiles in lungs.

The sensitivity to the fibrosis-inducing effect of bleomycin varies considerably from species to species, the reasons for which are unknown. The variability of the response in different strains of mice is well documented. Recent evidence indicates that the upregulated expression of cytokines and cytokine receptors may be involved. We evaluated the expression pattern of some cytokines and their receptors in C57Bl/6J bleomycin-sensitive and Balb/C bleomycin-resistant mice. Animals from both strains received, under ether anesthesia, either saline (50 microl) or bleomycin (0.1 U/50 microl) intratracheally. At various times after the treatment, the lungs were analyzed for cytokines and cytokine receptors by histochemistry and their mRNA by RNase protection assay. A significantly increased expression of TNF-alpha and IL-1beta was observed in both strains. However, an upregulated lung expression for TNF-alpha and IL-1 receptors was observed in C57Bl/6J-sensitive animals only. This profile is evident from 63 h onward. In addition to TNF-alpha, bleomycin administration also resulted in the upregulated expression of TGF-beta in the lungs of both strains at 8 h and in an enhanced expression of TGF-beta receptors I and II in C57Bl/6J mice only. The upregulation of TGF-beta receptor expression was preceded in this strain by an increased expression of IL-4, IL-13, and IL-13 receptor-alpha (at 8 h after bleomycin) and followed by an upregulation of gp130 and IL-6. The difference we observed in the cytokine receptor profile may offer an additional explanation for the different fibrogenic response of the two mouse strains to bleomycin.

Animals↗
PubMed2004

Essential role for cathepsin D in bleomycin-induced apoptosis of alveolar epithelial cells.

Our earlier studies showed that bleomycin-induced apoptosis of type II alveolar epithelial cells (AECs) requires the autocrine synthesis and proteolytic processing of angiotensinogen into ANG II and that inhibitors of ANG-converting enzyme (ACEis) block bleomycin-induced apoptosis (Li X, Zhang H, Soledad-Conrad V, Zhuang J, and Uhal BD. Am J Physiol Lung Cell Mol Physiol 284: L501-L507, 2003). Given the documented role of cathepsin D (CatD) in apoptosis of other cell types, we hypothesized that CatD might be the AEC enzyme responsible for the conversion of angiotensinogen into ANG I, the substrate for ACE. Primary cultures of rat type II AECs challenged with bleomycin in vitro showed upregulation and secretion of CatD enzymatic activity and immunoreactive protein but no increases in CatD mRNA. The aspartyl protease inhibitor pepstatin A, which completely blocked CatD enzymatic activity, inhibited bleomycin-induced nuclear fragmentation by 76% and reduced bleomycin-induced caspase-3 activation by 47%. Antisense oligonucleotides against CatD mRNA reduced CatD-immunoreactive protein and inhibited bleomycin-induced nuclear fragmentation by 48%. A purified fragment of angiotensinogen (F1-14) containing the CatD and ACE cleavage sites, when applied to unchallenged AEC in vitro, yielded mature ANG II peptide and induced apoptosis. The apoptosis induced by F1-14 was inhibited 96% by pepstatin A and 77% by neutralizing antibodies specific for CatD (both P < 0.001). These data indicate a critical role for CatD in bleomycin-induced apoptosis of cultured AEC and suggest that the role(s) of CatD in AEC apoptosis include the conversion of newly synthesized angiotensinogen to ANG II.

Angiotensin II↗
PubMed2006

Regression of high-grade malignancy in mice by bleomycin and interleukin-12 electrochemogenetherapy.

PURPOSE: Bleomycin electrochemotherapy has been successfully used in preclinical studies and clinical trials for treating squamous cell carcinoma (SCC) and adenocarcinoma; however, it is not effective for treating recurrent tumors or metastatic tumors, or for preventing tumor redevelopment. In this study, we explore the coadministration of bleomycin and interleukin-12 (IL-12) followed by electroporation for treating primary and metastatic tumors. EXPERIMENTAL DESIGN: Bleomycin, IL-12 plasmid DNA, or a combination of both were injected into high-grade malignant mammary tumors and SCCVII followed by electroporation. The tumor growth, survival, metastasis in lungs, CTL activity, and vascular density were analyzed. The results were analyzed by the two-sided Student's t test and Gehan's Wilcoxon test. RESULTS: Coadministration of bleomycin and IL-12 via electroporation eradicates preestablished 4T1 mammary tumors in up to 60% of mice, inhibits metastatic tumor development, and extends the long-term survival. Likewise, coadministration of bleomycin and IL-12 via electroporation eradicates squamous cell carcinoma (SCCVII) in 100% of mice and prevents tumor redevelopment in 80% of mice. Neither bleomycin nor IL-12 alone is able to achieve the same therapeutic potency. The primary role of bleomycin is to inhibit the tumor vessel development; the primary role of IL-12 is to increase the immune response that extends the survival of treated mice and inhibits the tumor redevelopment. CONCLUSIONS: This combination modality has great potential to be translated in a clinical setting for treating high-grade malignancies and for preventing tumor redevelopment.

Animals↗
PubMed2002

Preliminary exploration of the clinical effect of bleomycin on craniopharyngiomas.

OBJECTIVE: To investigate the antitumor effect of bleomycin on craniopharyngiomas. METHODS: A series of cystic craniopharyngiomas were randomly divided into three groups: (A) intracystic chemotherapy with bleomycin; (B) intracystic chemo-radiotherapy with bleomycin and (32)P; (C) intracystic radiotherapy with (32)P and 0.9% saline. The agents were injected into the cysts through stereotactically inserted silicone tubes. Follow-up was done for a minimum of 6 months. Outcome was based on a comparison of the volume of cysts before treatment and at follow-up. The index and lactate dehydrogenase (LD) of the cystic fluids, blood and cerebrospinal fluids and the endocrine function of these patients were determined before and after therapy. RESULTS: 19 patients finished the whole therapeutic course: 5 from group A, 9 from group B and 5 from group C. Four tumors in group A were polycystic, and the drug was selectively injected into the largest cyst. At follow-up, the volumes of the cysts in groups A and B regressed from 92 to 0%, while the drug-free cysts enlarged. In group B, 6 cysts almost disappeared and another 3 regressed from 78 to 57%. In group C, one cyst progressed and the others shrank by different degrees, but none disappeared completely or nearly. All patients in groups A and B had fever of different degrees, which resolved spontaneously in 8-24 h. The complications in group B included hyponatremia in 1 patient, and both adephagia obesity and cerebral infarction in 2 patients (1 of whom died after 6 months). Apart from the oculomotor paralysis occurring in 1 patient, the remainder of group C had no other severe complications. Blood chemistry, liver, kidney, pituitary and endocrinal functions changed little during the course in all these 19 patients. LD and its isoenzymes from the cystic fluids, CSF and serum showed no marked change after bleomycin injection. CONCLUSION: Bleomycin injected into cysts of craniopharyngiomas causes the tumor to shrink. When (32)P is added, the therapeutic effect seems better than treatment with either (32)P or bleomycin alone. Blood chemistry, liver, kidney and endocrine functions change little irrespective of the therapy applied. However, the combination of chemotherapy and radiotherapy may severely disturb both serum electrolytes and endocrine function. LD and its isoenzymes in the cystic fluids, CSF and serum may not change after bleomycin treatment.

Adolescent↗