Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis.

The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to-mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth. RAGE knockdown with multiple independent shRNAs in breast cancer cells led to decreased transwell invasion and soft agar colony formation, without affecting proliferation. In vivo, targeting RAGE shRNA knockdown in human and mouse breast cancer cells, decreased orthotopic tumor growth, reduced tumor angiogenesis and recruitment of inflammatory cells, and markedly decreased metastasis to the lung and liver in multiple xenograft and syngeneic mouse models. To test the non-tumor cell microenvironment role of RAGE, we performed syngeneic studies with orthotopically injected breast cancer cells in wild-type and RAGE-knockout C57BL6 mice. RAGE-knockout mice displayed striking impairment of tumor cell growth compared with wild-type mice, along with decreased mitogen-activated protein kinase signaling, tumor angiogenesis and inflammatory cell recruitment. To test the combined inhibition of RAGE in both tumor cell-intrinsic and non-tumor cells of the microenvironment, we performed in vivo treatment of xenografted tumors with FPS-ZM1 (1 mg/kg, two times per week). Compared with vehicle, FPS-ZM1 inhibited primary tumor growth, inhibited tumor angiogenesis and inflammatory cell recruitment and, most importantly, prevented metastasis to the lung and liver. These data demonstrate that RAGE drives tumor progression and metastasis through distinct tumor cell-intrinsic and -extrinsic mechanisms, and may represent a novel and therapeutically viable approach for treating metastatic cancers.

SIRT2 regulates tumour hypoxia response by promoting HIF-1α hydroxylation.

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that has a central role in the regulation of tumour metabolism under hypoxic conditions. HIF-1α stimulates glycolytic energy production and promotes tumour growth. Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular metabolism in response to stress; however, their involvement in the hypoxic response remains unclear. In this study, it is shown that SIRT2-mediated deacetylation of HIF-1α regulates its stability in tumour cells. SIRT2 overexpression destabilized HIF-1α under hypoxic conditions, whereas HIF-1α protein levels were high in SIRT2-deficient cells. SIRT2 directly interacted with HIF-1α and deacetylated Lys709 of HIF-1α. Deacetylation of HIF-1α by SIRT2 resulted in increased binding affinity for prolyl hydroxylase 2, a key regulator of HIF-1α stability, and increased HIF-1α hydroxylation and ubiquitination. Moreover, a pharmacological agent that increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF-1α by increasing SIRT2-mediated deacetylation and subsequent hydroxylation. These findings suggest that SIRT2-mediated HIF-1α deacetylation is critical for the destablization of HIF-1α and the hypoxic response of tumour cells.

Augmentation of NAD(+) by NQO1 attenuates cisplatin-mediated hearing impairment.

Cisplatin (cis-diaminedichloroplatinum-II) is an extensively used chemotherapeutic agent, and one of its most adverse effects is ototoxicity. A number of studies have demonstrated that these effects are related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as a key regulator of cellular energy metabolism and homeostasis. Here, we demonstrate for the first time that, in cisplatin-mediated ototoxicity, the levels and activities of SIRT1 are suppressed by the reduction of intracellular NAD(+) levels. We provide evidence that the decrease in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) transferase (PARP)-1 activation and microRNA-34a through p53 activation aggravates cisplatin-mediated ototoxicity. Moreover, we show that the induction of cellular NAD(+) levels using ß-lapachone (ß-Lap), whose intracellular target is NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity.

A quantitative evaluation method of skin texture affected by skin ageing using replica images of the cheek.

OBJECTIVE: Skin texture is a fine structure of skin surface where the hill and furrow were crossed to form a star shape. This study was performed to establish a quantitative evaluation method of skin texture affected by skin ageing using replica images of the cheek. METHODS: After producing replicas of the left cheek areas of 80 female subjects, representative replica images were chosen to establish six-level facial skin texture index. Using this new index, skin texture of different-aged subjects was visually assessed by multiple examiners. The number of star configurations was also analysed using the same replica images. Other factors contributing to skin texture, such as skin elasticity, roughness, dermal density, moisture and gloss, were also analysed. RESULTS: The concordance between skin texture scores evaluated by three researchers was high (0.896), and there was a high correlation between skin texture score and age (r = 0.642). The number of star configurations showed high correlations with skin texture scores (r = 0.753) and with age (r = 0.776). Skin texture scores were highly correlated with skin roughness and dermal density, but not with moisture, gloss and elasticity. CONCLUSION: This study suggests that visual grading of skin texture score based on new facial skin texture index and quantification of star configurations will be useful in evaluating skin ageing.

A capture-recapture model of amphidromous fish dispersal.

Adult movement scale was quantified for two tropical Caribbean diadromous fishes, bigmouth sleeper Gobiomorus dormitor and mountain mullet Agonostomus monticola, using passive integrated transponders (PITs) and radio-telemetry. Large numbers of fishes were tagged in Río Mameyes, Puerto Rico, U.S.A., with PITs and monitored at three fixed locations over a 2·5 year period to estimate transition probabilities between upper and lower elevations and survival probabilities with a multistate Cormack-Jolly-Seber model. A sub-set of fishes were tagged with radio-transmitters and tracked at weekly intervals to estimate fine-scale dispersal. Changes in spatial and temporal distributions of tagged fishes indicated that neither G. dormitor nor A. monticola moved into the lowest, estuarine reaches of Río Mameyes during two consecutive reproductive periods, thus demonstrating that both species follow an amphidromous, rather than catadromous, migratory strategy. Further, both species were relatively sedentary, with restricted linear ranges. While substantial dispersal of these species occurs at the larval stage during recruitment to fresh water, the results indicate minimal dispersal in spawning adults. Successful conservation of diadromous fauna on tropical islands requires management at both broad basin and localized spatial scales.

Otolith microchemistry of tropical diadromous fishes: spatial and migratory dynamics.

Otolith microchemistry was applied to quantify migratory variation and the proportion of native Caribbean stream fishes that undergo full or partial marine migration. Strontium and barium water chemistry in four Puerto Rico, U.S.A., rivers was clearly related to a salinity gradient; however, variation in water barium, and thus fish otoliths, was also dependent on river basin. Strontium was the most accurate index of longitudinal migration in tropical diadromous fish otoliths. Among the four species examined, bigmouth sleeper Gobiomorus dormitor, mountain mullet Agonostomus monticola, sirajo goby Sicydium spp. and river goby Awaous banana, most individuals were fully amphidromous, but 9-12% were semi-amphidromous as recruits, having never experienced marine or estuarine conditions in early life stages and showing no evidence of marine elemental signatures in their otolith core. Populations of one species, G. dormitor, may have contained a small contingent of semi-amphidromous adults, migratory individuals that periodically occupied marine or estuarine habitats (4%); however, adult migratory elemental signatures may have been confounded with those related to diet and physiology. These findings indicate the plasticity of migratory strategies of tropical diadromous fishes, which may be more variable than simple categorization might suggest.

Long-term effects of glans penis augmentation using injectable hyaluronic acid gel for premature ejaculation.

The authors created the glans penis augmentation by injectable hyaluronic acid gel and reported the 6-month result for premature ejaculation. In a total of 38 patients, long-term effects of 5 years were compared to those of 6 months in terms of residual volume of implants and efficacy on premature ejaculation. Maximal glandular circumference measured by tapeline significantly decreased by 15% (P<0.05) but mean patient's visual estimation (Gr 0-Gr 4) did not decrease (3.60 vs 3.56, P>0.05). Compared to 6-month follow-up, intravaginal ejaculatory latency time and vibratory threshold decreased at 5 years (P<0.05), but still well increased considering those of preaugmentation. Hence, 76% of patients and 63% of partners were still satisfied. There was no serious adverse reaction. In the 5-year long-term follow-up of glans penis augmentation by filler, the implants were well maintained and effective for glans penis hypersensitivity in premature ejaculation patients.

CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling.

The carcinoembryonic antigen (CEAs) family consists of a large group of evolutionarily and structurally divergent glycoproteins. The transforming growth factor-beta (TGF-beta) signaling pathway has been implicated in the stimulation of CEA secretion in TGF-beta-sensitive colon cells, thereby possibly modulating cell adhesion and differentiation. However, the specific CEAs targeted by TGF-beta signaling or underlying mechanism of the expression of CEAs has not yet been clarified. In this study, we investigated the specific CEAs targeted by the TGF-beta signaling pathway. In nine human gastric cancer cell lines examined, TGF-beta-responsive cell lines showed positive expression of CEAs. Expression patterns of CEA proteins correlated well with the level of CEA (CEACAM5) and CEACAM6 transcripts in these cell lines, but CEACAM1 expression was not observed in all of these cells. To investigate the role of TGF-beta signaling in CEA expression, we selected two TGF-beta unresponsive gastric cancer cell lines; SNU638 cells that contain a mutation in the TGF-beta type II receptor and SNU484 cells that express low to undetectable level of the TGF-beta pathway intermediate protein, Smad3. Restoration of TGF-beta signaling in these cells induced expression of the CEAs and increased activity of both CEA (CEACAM5) and CEACAM6 promoters. CEA expression was observed in the epithelium of the stomach of wild-type mice, but was markedly decreased in Smad3 null mice. These findings suggest that CEA (CEACAM5) and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling.

Effects of glans penis augmentation using hyaluronic acid gel for premature ejaculation.

The main limitation of medical treatment for premature ejaculation is recurrence after withdrawal of medication. We evaluated the effect of glans penis augmentation using injectable hyaluronic acid (HA) gel for the treatment of premature ejaculation via blocking accessibility of tactile stimuli to nerve receptors. In 139 patients of premature ejaculation, dorsal neurectomy (Group I, n=25), dorsal neurectomy with glandular augmentation (Group II, n=49) and glandular augmentation (Group III, n=65) were carried out, respectively. Two branches of dorsal nerve preserving that of midline were cut at 2 cm proximal to coronal sulcus. For glandular augmentation, 2 cc of HA was injected into the glans penis, subcutaneously. At 6 months after each procedure, changes of glandular circumference were measured by tapeline in Groups II and III. In each groups, ejaculation time, patient's satisfaction and partner's satisfaction were also assessed. There was no significant difference in preoperative ejaculation time among three groups. Preoperative ejaculation times were 89.2+/-40.29, 101.54+/-59.42 and 96.5+/-52.32 s in Groups I, II and III, respectively. Postoperative ejaculation times were significantly increased to 235.6+/-58.6, 324.24+/-107.58 and 281.9+/-93.2 s in Groups I, II and III, respectively (P<0.01). The percentage of postoperative satisfaction in both patient and his partner was 68% (17/25) and 44% (7/16) in Group I, 80% (39/49) and 66% (25/38) in Group II and 75% (49/65) and 62% (32/52) in Group III, respectively. Maximal glandular girth was significantly increased from 9.16+/-0.59 to 10.95+/-0.4 cm in Group II and 8.95+/-0.54 to 11.67+/-0.71 cm in Group III, respectively. These results suggest that glandular augmentation with injectable HA gel is a safe and effective modality to reduce sensory of glans penis. Long-term follow-up for residual volume and efficacy should be requested to establish its precise therapeutic potentials in premature ejaculation.

Human glans penis augmentation using injectable hyaluronic acid gel.

Although augmentation phalloplasty is not an established procedure, some patients still need enlargement of their penis. Current penile augmentation is girth enhancement of penile body by dermofat graft. We performed this study to identify the efficacy and the patient's satisfaction of human glans penis augmentation with injectable hyaluronic acid gel. In 100 patients of subjective small penis (Group I) and 87 patients of small glans after dermofat graft (Group II), 2 cm(3) of hyaluronic acid gel was injected into the glans penis, subcutaneously. At 1 y after injection, changes of glandular diameter were measured by tapeline. Patient's visual estimation of glandular size (Gr 0-4) and patient's satisfaction (Grade (Gr) 0-4) were evaluated, respectively. Any adverse reactions were also evaluated. The mean age of patients was 42.2 (30-70) y in Group I and 42.13 (28-61) y in Group II. The maximal glandular circumference was significantly increased compared to basal circumference of 9.13+/-0.64 cm in Group I (P<0.01) and 9.49+/-1.05 cm in Group II (P<0.01) at 1 y after injection. Net increase of maximal glandular circumference after glans augmentation was 14.93+/-0.80 mm in Group I and 14.78+/-0.89 mm in Group II. In patient's visual estimation, more than 50% of injected volume was maintained in 95% of Group 1 and 100% of Group II. The percentage of postoperative satisfaction (Gr 4, 5) was 77% in Group 1 and 69% in Group II. There was no abnormal reaction in area feeling, texture, and color. In most cases, initial discoloration by glandular swelling recovered to normal within 2 weeks. There were no signs of inflammation and no serious adverse reactions in all cases. These results suggest that injectable hyaluronic acid gel is a safe and effective material for augmentation of glans penis.

Augmentation of glans penis using injectable hyaluronic acid gel.

Recently, injectable hyaluronic acid gel has been widely used in soft-tissue augmentation. We performed this study to identify the feasibility of hyaluronic acid gel for the augmentation of the glans penis. In experiment I, 0.2 cm(3) of hyaluronic acid gel (HA) was injected into the dermis of the glans penis of 25 New Zealand white rabbits via a 30 G needle. At 3, 7, 14, 30, and 90 days after injection, histological changes of glans were studied, respectively. In experiment II, 0.5 cm(3) of HA was injected into the dermis of the glans penis of 14 Beagle dogs via a 27 G needle. At 6 months after injection, histological changes of the glans penis were also evaluated. At the time of autopsy, the lung, liver, and spleen were studied for systemic adverse reaction in each separate experiment. In experiment I, various sized cavities filled with amorphous basophilic materials were noted in the lamina propria and corpus spongiosum of the glans penis. All implants were positively stained on alcian blue. The intensity decreased in a time-dependent manner. Until 14 days, minimal inflammatory reactions were noted, but no signs of inflammation were identified at 90 days. With the gradual decrease of inflammation, fibrosis and deposition of collagen were noted. In experiment II, implants were well maintained at 6 months after injection in the lamina propria. Grade 1 of the inflammatory reaction was noted in one case. In both the experiments, all the specimens were free from any foreign body reaction and systemic adverse reactions. In conclusion, these results suggest that hyaluronic acid gel can be easily injected into the lamina propria of the glans penis and reside until 6 months. Injectable hyaluronic acid gel has a potential as a new bioimplant for the augmentation of the glans penis.

Anti-lipid peroxidative principles from the stem bark of Kalopanax pictus Nakai.

Hepatic lipid peroxide contents were examined in bromobenzene-treated rats firstly after the oral administration of MeOH extract of Kalopanax pictus stem barks, its n-BuOH fraction, EtOAc fraction and an alkaline hydrolysate of the n-BuOH fraction, and secondly after the intraperitoneal administration of hederagenin monodesmosides and bisdesmosides. Two hederagenin monodesmosides, kalopanaxsaponin A (KPS-A) and sapindoside C, exhibited significant anti-lipid peroxidation effects after intraperitoneal administration at doses of 10-30 micromole/kg, whereas their bisdesmosides did not exhibit any significant activity. These results suggest that it is the hederagenin monodesmosides that are responsible for anti-lipid peroxidation in vivo. The activity of KPS-A was established by the observation of decreased aminopyrine N-demethylase activity and increased epoxide hydrolase activity.

Clinical features and surgical outcome in patients with asymptomatic meningiomas.

The clinical features and surgical outcomes of 108 patients with an asymptomatic meningioma were studied in patients who were admitted to any neurosurgical institute in the Yamaguchi prefecture in the southern part of Japan between 1986 and 1995. Their clinical characteristics were compared with 414 patients with symptomatic meningiomas over the same period. Asymptomatic patients were older than symptomatic patients, although not significantly so. Tumours were located in the right cerebral hemisphere (46 versus 31%, p = 0.003) more frequently in asymptomatic than in symptomatic patients. Four of 75 surgically-treated asymptomatic patients had a poor outcome, including two with severe disability and two deaths. Such outcomes did not differ significantly in frequency compared with those of 356 surgically-treated symptomatic patients which included 11 with severe disability and 11 deaths. Postoperative morbidity and mortality in asymptomatic patients are not negligible. Poor outcome was associated with more advanced age and with midline tumours.

Intracranial metastasis of Wilms' tumor involving the tectal plate without pulmonary involvement. Case report.

Intracranial metastasis without pulmonary involvement of Wilms' tumor is very rare, and most previously reported metastatic sites have been in the cerebral parenchyma. We experienced a rare case of metastasis of Wilms' tumor in the tectal plate without pulmonary involvement. A 3-month-old boy was admitted to our hospital due to hydrocephalus. After insertion of a ventriculoperitoneal shunt, there were no neurological deficits. Five months after the operation, a mass 5 cm in diameter extending from the tectal plate into the third ventricle was found. A mass 10 cm in diameter within the retroperitoneal space, which occupied the right kidney, was also found. Both tumors were resected and diagnosed histologically as Wilms' tumor. Despite every effort including chemotherapy and radiotherapy, the patient died at 14 months old. The majority of children with hydrocephalus showing thickening of the tectal plate would most likely have tectal glioma; however, this unusual case report reminds us that metastasis of Wilms' tumor can occur in the tectal plate causing hydrocephalus.

Inhibitory effects of propiverine, atropine and oxybutynin on bladder instability in rats with infravesical outlet obstruction.

OBJECTIVE: To compare the inhibitory effects of propiverine HCl(BUP-4) with those of atropine and oxybutynin on the detrusor instability induced by partial obstruction of the bladder neck of female rats. MATERIALS AND METHODS: Partial obstruction was created using partial ligation of the proximal urethra in 20 female Sprague-Dawley rats. Both the obstructed rats and a control group of 15 rats were evaluated cystometrically about 6 weeks later and the values compared both baseline and after injection with BUP-4, atropine or oxybutynin. During cystometry, the bladder capacity (BC), residual volume (RV), compliance and frequency of spontaneous activity (SA) were determined. RESULTS: The BC, RV and frequency of SA were significantly increased, and compliance markedly decreased, in obstructed compared with normal rats. The micturition pressure was significantly decreased only after injection with BUP-4 in both normal and obstructed rats. For both, the BC was increased significantly after injection with atropine or BUP-4 (P < 0.05), with the increase greater after BUP-4 than after atropine in both groups (P < 0.01). After injecting BUP-4, the RV was significantly increased in both groups (P < 0.05); atropine increased the RV only in normal rats (P < 0.01) and oxybutynin had no significant effect on RV. Increases in compliance after the administration of each drug were significant only in obstructed rats (P < 0.01) and were markedly higher after oxybutynin (780%) than after the other drugs (180-250%). The frequencies and amplitude of SA after injection with each drug were significantly lower only in obstructed rats, but in these rats, there were no significant differences in this reduction after injecting oxybutynin or BUP-4, whereas they were significantly greater after injecting oxybutynin than after atropine. CONCLUSION: Partial bladder outlet obstruction successfully created a hyperactive (unstable) bladder, typified by increased BC, RV, frequency of SA and a marked decrease in compliance. The greater BC, lower MP and frequency and amplitude of SA were prominent after the administration of BUP-4. Thus it is suggested that BUP-4 effectively inhibited bladder instability in rats induced by infravesical outlet obstruction and was more effective than oxybutynin in increasing BC.

Pilocytic astrocytoma of the velum interpositum.

A 72-year-old male presented with a pilocytic astrocytoma in the velum interpositum manifesting as a 5-day history of dizziness attacks and unstable gait. Computed tomography and T1-weighted magnetic resonance imaging with gadolinium enhancement demonstrated a small, homogeneously enhanced mass in the velum interpositum. The tumor was removed subtotally, and the structure of the splenium was intact. The histological diagnosis was pilocytic astrocytoma. The MIB-1 growth fraction was 5%. The tumor may have originated from the splenium or the thalamus. The aggressive histology indicates the need for close neuroimaging follow-up.

Selective extradural anterior clinoidectomy for supra- and parasellar processes. Technical note.

Removal of the anterior clinoid process (ACP) facilitates radical removal of tumors or radical neck clipping of aneurysms in the supra- and parasellar regions by providing a wide operative exposure of the internal carotid artery (ICA) and the optic nerve and by reducing the need for brain retraction. Over a period of 3 years, anterior clinoidectomy was performed in 40 patients, 30 of whom harbored aneurysms (18 of the ICA and 13 of the basilar artery [one patient had two aneurysms]) and 10 of whom had tumors (four large pituitary tumors, four craniopharyngiomas, and two sphenoid ridge meningiomas). The ACP was removed extradurally in 31 cases and intradurally in nine cases. Extradural clinoidectomy was performed in all cases of pituitary adenoma and craniopharyngioma and in most cases of basilar artery aneurysm. Intradural clinoidectomy was performed in two cases of ICA-ophthalmic artery aneurysm, two cases of ICA-posterior communicating artery aneurysm, two cases of ICA cavernous aneurysm, one case of basilar artery aneurysm, and two cases of sphenoid ridge meningioma. The outcome was satisfactory in all patients, except for one patient who underwent clipping of a basilar tip aneurysm and suffered a thalamic and midbrain infarction. Three patients who underwent extradural clinoidectomy suffered a postoperative diminution of visual acuity or a visual field defect on the side of the clinoidectomy. These deficits may have been caused either by drilling of the ACP or by other operative manipulation of the optic nerve. Cerebrospinal fluid rhinorrhea, which required reoperation, occurred in one patient. The authors' experience suggests that the extradural technique of ACP removal is easier and less time consuming than the intradural one and provides better operative exposure. It can be used routinely in treating lesions in the supra- and parasellar regions.

Food web analysis of southern California coastal wetlands using multiple stable isotopes.

Carbon, nitrogen, and sulfur stable isotopes were used to characterize the food webs (i.e., sources of carbon and trophic status of consumers) in Tijuana Estuary and San Dieguito Lagoon. Producer groups were most clearly differentiated by carbon, then by sulfur, and least clearly by nitrogen isotope measurements. Consumer 15N isotopic enrichment suggested that there are four trophic levels in the Tijuana Estuary food web and three in San Dieguito Lagoon. A significant difference in multiple isotope ratio distributions of fishes between wetlands suggested that the food web of San Dieguito Lagoon is less complex than that of Tijuana Estuary. Associations among sources and consumers indicated that inputs from intertidal macroalgae, marsh microalgae, and Spartina foliosa provide the organic matter that supports invertebrates, fishes, and the light-footed clapper rail (Rallus longirostris levipes). These three producers occupy tidal channels, low salt marsh, and mid salt marsh habitats. The only consumer sampled that appears dependent upon primary productivity from high salt marsh habitat is the sora (Porzana carolina). Two- and three-source mixing models identified Spartina as the major organic matter source for fishes, and macroalgae for invertebrates and the light-footed clapper rail in Tijuana Estuary. In San Dieguito Lagoon, a system lacking Spartina, inputs of macroalgae and microalgae support fishes. Salicornia virginica, S. subterminalis, Monanthochloe littoralis, sewage- derived organic matter, and suspended particulate organic matter were deductively excluded as dominant, direct influences on the food web. The demonstration of a salt marsh-channel linkage in these systems affirms that these habitats should be managed as a single ecosystem and that the restoration of intertidal marshes for endangered birds and other biota is compatible with enhancement of coastal fish populations; heretofore, these have been considered to be competing objectives.

Detection of structural aberrations of chromosome 17 in malignant gliomas by fluorescence in situ hybridization (FISH).

Isolated nuclei prepared from fresh-frozen tissue specimens were used to investigate structural aberrations of chromosome 17 in 18 malignant gliomas (7 anaplastic astrocytomas, 11 glioblastomas). Nuclear DNA was hybridized with four DNA probes specific for centromeric (D17ZI), telomeric (Tel 17p, Tel 17q) and 17p 13.1 sequences (p53) of chromosome 17, using fluorescence in situ hybridization (FISH). The rates of nuclei with one signal (OS) for Tel 17p and p53 were significantly higher than those for D17ZI and Tel 17q. This indicated that the majority of chromosome 17 aberrations was a deletion of the short arm including the p53 gene. When compared with the histological grading, the rates of OS for Tel 17p and p53 in anaplastic astrocytomas were higher than those of glioblastomas, suggesting that the deletion may be associated with the early events in tumorigenesis and that some glioblastomas without chromosome 17 aberrations may be independent from tumour progression via low-grade gliomas.