The TriAGe+ Score for Vertigo or Dizziness: A Diagnostic Model for Stroke in the Emergency Department.

BACKGROUND: Vertigo or dizziness is a common occurrence, but it remains a challenging symptom when encountered in the emergency department (ED). A diagnostic score for stroke with high accuracy is therefore required. METHODS: A single-center observational study (498 patients) was conducted. The predictor variables were derived from a multivariate logistic regression analysis with Akaike information criterion. The outcome was the occurrence of stroke. We evaluated the utility of a new diagnostic score (TriAGe+) and compared it with the ABCD2 score. RESULTS: The cohorts included 498 patients (147 with stroke [29.4%]). Eight variables were included: triggers, atrial fibrillation, male gender, blood pressure ≥140/90 mm Hg, brainstem or cerebellar dysfunction, focal weakness or speech impairment, dizziness, and no history of vertigo or dizziness or labyrinth or vestibular disease. We derived the TriAGe+ score from these variables. In the cohort, the prevalence of stroke increased significantly using the diagnostic score: 5.9% for a score of 0-4; 9.1% for 5-7; 24.7% for 8-9; and 57.3% for 10-17. At a cutoff value of 10 points, the sensitivity of the score was 77.5%, the specificity was 72.1%, and the positive likelihood ratio was 3.2. When the cutoff was defined as 5 points, the score obtained a high sensitivity (96.6%) with a good negative likelihood ratio (.15). The new score outperformed the ABCD2 score for the occurrence of stroke (C statistic, .818 versus .726; P < .001). CONCLUSIONS: The TriAGe+ score can identify the occurrence of stroke in patients with vertigo or dizziness presenting to the ED.

Websites offer helpful information concerning consultation with headache specialists.

Patients with severe primary headache may benefit from consultation with headache specialists, but doctor attendance rates in Japan are very low. More headache patients might consult headache specialists if these specialists were more widely recognized by the public. To determine what information prompted patients to seek consultation with a headache specialist, we questioned 256 primary headache patients about the source of the helpful information concerning consultation with headache specialists. From 191 patients, a total of 235 responses to the questionnaire were obtained. The most common response was 'websites' (33.2%), followed by 'professionals' (23.8%), 'acquaintances' (20.9%), 'print media' (6.8%) and 'TV/radio' (3.4%). Patients who indicated websites showed the most severe pain and highest impact of headache, and accounted for 52.4% of those with cluster headaches. Development of websites concerning headache specialists would seem likely to increase doctor attendance rates for patients with primary headache.

Controlling tumor angiogenesis and metastasis of C26 murine colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models.

Experimental evidence has directly implicated matrix metalloproteinases (MMPs) in the remodeling of the stromal tissue surrounding tumors. Thus, MMP inhibitors could limit the expansion of both neoplastic cell compartment and endothelial cell compartment of a tumor. Much of the work on the role of MMP inhibitors has concentrated on their inhibitory effects on tumor cell invasion. We have examined the effects of a new MMP inhibitor, KB-R7785 (acting on MMP-1, MMP-3, and MMP-9), on tumor angiogenesis and metastasis of murine colon adenocarcinoma (C-26) in two tumor models in BALB/c mice (transparent chamber model and lung colonization model). KB-R7785 has not shown inhibitory effects on in vitro growth of either C-26 or KOP2.16 murine endothelial cells. In vivo, KB-R7785 administrated twice daily for 15 days (100 mg/kg, i.p.), starting the day of tumor inoculation (5 x 10(5) C26 cells) in transparent chamber, has resulted in 88.2% suppression of tumor growth, compared with that in vehicle-administered mice (controls). Tumors grown in controls have doubled their area in 3.3 days, whereas those treated by KB-R7785 progressed almost four times slower (tumor area doubling time, 12 days). KB-R7785 rendered centrally avascular tumors with only a rim of peripheral neovasculature, which had significant lower functional vascular density and vascular area than the corresponding parameters in control tumors 10 days after inoculation [79.9+/-6.7 cm/cm2 versus 164.1+/-10.1 cm/cm2 (P < 0.01) and 19.8+/-1.5% versus 42.6+/-2.7% (P < 0.01), respectively]. In the lung colonization model (tail vein inoculation of 5 x 10(5) C-26 cells), administration of KB-R7785 (100 mg/kg, i.p.) twice daily for 20 days has reduced the number of surface metastasis by 85.8% and abolished the tumor burden, as compared with controls. The few metastatic colonies found in the lungs of KB-R7785 treated mice appeared to be dormant (i.e., staining with von Willebrand factor antibody revealed few, if any, positive cells within the metastatic foci from MMP inhibitor-treated lungs, whereas terminal deoxynucleotidyl transferase-mediated nick end labeling showed a 4-fold increase in the rate of tumor cell apoptosis compared with controls. The fact that KB-R7785 interferes with early steps of angiogenesis and cancer spread suggests that MMP inhibitors may control both primary and secondary tumor growths by limiting the expansion of endothelial cells, as well as cancer cells, composing the tumors.

Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis.

Cytogenetic and molecular studies demonstrated that pancreatic cancer frequently shows specific chromosomal abnormalities, such as losses of 9p, 17p, and 18q, and gains of 8q and 20q. We have analyzed alterations in the copy number of specific chromosomal regions in cells from the pancreatic juices of 32 patients with various pancreatic disorders by fluorescence in situ hybridization (FISH) technique to pursue the possible clinical use of early diagnosis of pancreatic cancer. None of the chromosomal abnormalities were found in 13 specimens from individuals who had no neoplastic lesions. On the other hand, 12 specimens (63%) derived from the remaining 19 patients who had neoplastic lesions showed at least one chromosomal abnormality. Ten of these specimens were from pancreatic cancer patients; 7 cases (70%) showed chromosomal abnormalities. All but one of the 12 tumors with chromosomal abnormalities had loss of 18q. Furthermore, we detected a tumor in one patient in whom the routine cytological method and endoscopic retrograde chorangiopancreatography found nothing. Based on the results by FISH, we performed endoscopic ultrasonography and found a small serous cystadenoma in this patient. These results indicate that: (a) FISH analysis of cells from pancreatic juices obtained during endoscopic retrograde chorangiopancreatography is quite useful for detecting pancreatic ductal tumors; and (b) loss of chromosome 18q is one of the early genetic changes that provide very useful information in diagnosing pancreatic neoplasias.

Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer.

Using the method of microsatellite analysis, we studied 40 tissues with pancreatic ductal adenocarcinoma and identified two commonly deleted regions on the long arm of chromosome 12. One (region A) was found between D12S81 and D12S1719 at 12q21 at a frequency of 67.5%, and the other (region B) was located between D12S360 and D12S78 at 12q22-q23.1 at a frequency of 60%; the latter was reported previously (M. Kimura, et al. Genes Chromosomes Cancer, 17: 88-93, 1996). The results of microsatellite analyses were verified by fluorescence in situ hybridization. We further analyzed 19 pancreatic cancer cell lines by fluorescence in situ hybridization and found that 10 of them showed allelic loss at D12S81 and 6 showed allelic loss at D12S360. Yeast artificial chromosome contigs were constructed to cover the deleted regions. Region B was completely covered by a 650-kb yeast artificial chromosome clone. The frequently deleted regions in chromosome 12q in pancreatic cancer that were identified here may provide new avenues for isolating novel tumor suppressor genes.

Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats. Part 1. Under normal resting conditions.

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the response of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 +/- 25 micron, mean +/- SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 +/- 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.

Comparison between the photoelectric method and H2 clearance method for measuring cerebrocortical blood flow in cats.

The photoelectric method using carbon black as a nondiffusible tracer of blood was compared with the hydrogen clearance (H2) method in nine anesthetized cats. A photoelectric apparatus and H2 electrode were applied to a small region of the cerebral cortex (left ectosylvian gyrus) for simultaneous measurement of the regional CBF. The values of CBF(H2) and CBF(photoelectric) were 50.7 +/- 19.2 and 52.1 +/- 14.5 ml.100 g-1.min-1, respectively. CBF(H2) and CBF(photoelectric) were found to correlate well (r = 0.588, p less than 0.01) when changes in CBF were induced by CO2 inhalation, exsanguination, hyperventilation, and occlusion of the middle cerebral artery. The correlation between CBF(H2) and CBF(photoelectric) was much better in the case of intraindividual comparisons (r = 0.957, p less than 0.01). In addition to its merits in common with the H2 clearance method, such as handiness, low cost, and strict regionality, the photoelectric method displayed the following advantages: time-to-time measurements of CBF (less than 20 s), immediate display of the microcirculatory flow pattern, and simultaneous monitoring of cerebral blood volume. However, measurements from deep structures of the brain are better performed by the H2 method despite the disadvantage of the use of a potentially explosive gas.

Blood flow velocity in the pial arteries of cats, with particular reference to the vessel diameter.

The blood flow velocity and diameter of feline pial arteries, ranging in diameter from 20 to 200 microns, were measured simultaneously using a newly developed video camera method under steady-state conditions for all other parameters. There was a linear relationship between blood flow velocity and pial artery diameter (y = 0.340x + 0.309), the correlation coefficient being 0.785 (p less than 0.001). The average values for blood flow velocity in pial arteries less than 50 microns, greater than or equal to 50 but less than 100 microns, greater than or equal to 100 but less than 150 microns, and greater than or equal to 150 microns in diameter were 12.9 +/- 1.3, 24.6 +/- 3.4, 42.1 +/- 4.7, and 59.9 +/- 5.3 mm/s, respectively. Blood flow rate was calculated as a product of the cross-sectional area and the flow velocity. The blood flow rate increased exponentially as the pial artery diameter increased (y = 2.71 X 10(-4) x2.98). The average values for blood flow rate in pial arteries less than 50 microns, greater than or equal to 50 but less than 100 microns, greater than or equal to 100 but less than 150 microns and greater than or equal to 150 microns in diameter were 12.8 +/- 1.5, 122.1 +/- 24.8, 510.2 +/- 74.8, and 1524.2 +/- 174.4 10(-3) mm3/s, respectively. Hemorheological parameters such as the wall shear rate and Reynolds' number were also calculated. The data obtained provide a useful basis for further investigations in the field of cerebral circulation.

Video camera method for simultaneous measurement of blood flow velocity and pial vessel diameter.

A new method for the simultaneous measurement of blood flow velocity and pial vessel diameter is described. The system consists basically of a high-sensitivity vidicon camera, camera control, width analyzer, video densitometer, TV monitor, desktop computer, and multi-pen recorder. The pial vessels are visualized through a cranial window at 25-200x magnification on the TV monitor. The diameter of three target vessels can be recorded simultaneously on the recorder by adjustment of controllable video signal gates using the width analyzer. At the same time, the optical densities of two targets at points upstream and downstream of the pial vessel are measured continuously with video densitometers, and their outputs are recorded on the polygraph and analyzed by the computer. The time difference in the two peaks of time--concentration curves, produced very 2-3 s at the highest frequency by the injection of a small amount of saline through the lingual artery, is measured on-line using the computer. The flow velocity in the vessel is calculated from the time difference and the distance between the two targets. The system was shown to be stable, reliable, and rapid in response. This method may provide a useful tool for research in the field of blood circulation in the brain or any other organ.

Constriction/dilatation of the cerebral microvessels by intravascular endothelin-1 in cats.

The effects of intracarotidly injected endothelin (ET)-1 (0.01-3 nmol) on the local cerebral blood volume (CBV) in the parietotemporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative dimensions of the cerebral microvessels. Low doses of ET-1 (0.01 and 0.1 nmol) elicited mild but significant reductions in CBV without changes in the systemic arterial blood pressure (SABP). High doses of ET-1 (3 nmol) initially induced marked declines of CBV, which were attributable to the significant falls in SABP. CBV subsequently exhibited significant increases. The CBV increases were not secondary to the accompanying elevations of SABP, since they were unaffected by inhibition of the SABP changes after preinjection of BQ-123 (1 mg/kg), an ET antagonist specific to the ETA receptors. The CBV increases, however, were prevented by continuous administration of NG-mono-methyl-L-arginine (0.35 mg/kg/min), an inhibitor of nitric oxide synthesis, plus BQ-123. We conclude that while low doses of intravascular ET-1 constrict the cerebral microvessels, high doses of ET-1 dilate the cerebral microvessels through the induction of nitric oxide probably in the cerebrovascular endothelium.

Effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels in cats.

To elucidate the fundamental actions of endogenous opioids and naloxone on the cerebral circulation, the effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels were investigated in cats. Pial arteries (165.7 +/- 24.9 microns) were found to dilate after the intravenous administration of 1 mg/kg of (D-Met2,Pro5)-enkephalinamide, and a definite dilatation of 7.1-7.6% persisted for 15 min. Pial veins (100.6 +/- 20.2 microns) also dilated but to a lesser degree. The MABP (118.7 +/- 10.5 mm Hg) decreased by 20 mm Hg immediately after the injection, but gradually returned to the initial value 15 min later. The observed cerebral vasodilatation may be attributable to sympathetic inhibition mediated either by the presynaptic opiate receptors of the cerebral vessels or by the opiate receptors in the brainstem. After the intravenous administration of 1 mg/kg of naloxone, pial arteries (122.0 +/- 17.2 microns) showed a slight but significant dilatation of 2.3-5.3%. There were no significant changes in pial veins (87.0 +/- 12.4 microns). MABP (130.4 +/- 12.3 mm Hg) was slightly increased after the injection. Although the mechanism involved was unclear, the cerebral vasodilatation occurring after the administration of naloxone may contribute to its ameliorating effect on the neurological symptoms following cerebral ischemia.

Leuko-araiosis, cerebral atrophy, and cerebral perfusion in normal aging.

To elucidate the role of leuko-araiosis observed on computed tomographic imaging among normal populations, 37 neurologically and cognitively normal volunteers ages 18 to 88 years were studied. Local cerebral blood flow was measured using stable xenon-enhanced computed tomography. Severity of leuko-araiosis and cerebral atrophy were graded on computed tomographic images. Leuko-araiosis was observed in 21.6% of normal volunteers, in 52.2% of patients with multi-infarct dementia (n = 23), and in 61.5% of patients with dementia of the Alzheimer type (n = 13). When multiple regression analysis was applied among normal volunteers, the degree of cerebral atrophy, advancing age, and local cerebral blood flow reductions of subcortical white matter correlated and contributed in that order of precedence to the presence and severity of leuko-araiosis. Combination of the unusual vascular anatomy of periventricular white matter together with cerebral hypoperfusion appears to be related to the occurrence of leuko-araiosis observed among neurologically and cognitively normal subjects. Further investigations should determine whether leuko-araiosis among this population is a risk factor for later cognitive impairments.

Local cerebral blood flow and its response to intravenous levodopa in progressive supranuclear palsy. Comparison with Parkinson's disease.

The local cerebral blood flow (LCBF) at steady state and after the intravenous administration of levodopa (1 mg/kg) was measured by the xenon-enhanced computed tomographic method in six patients with progressive supranuclear palsy (PSP) and in nine patients with idiopathic Parkinson's disease. The baseline LCBF values in most brain regions in patients with PSP were lower than those in patients with Parkinson's disease, and hyperfrontality of the LCBF was lost. In patients with Parkinson's disease, the injection of levodopa markedly increased LCBF, especially in the striatum, thalamus, and internal capsule (approximately 40%). In patients with PSP, however, levodopa did not increase the LCBF in all brain regions examined. The LCBF increases after the administration of levodopa in patients with Parkinson's disease may be secondary to metabolic activation of the dopaminergic system. The different LCBF responses to levodopa between patients with PSP and those with Parkinson's disease may reflect differences in pathologic features, such as in the degree of preservation of nigrostriatal dopaminergic neurons and the distribution and density of dopamine receptors, and are also related to the clinical effectiveness of levodopa therapy.

Familial idiopathic brain calcification with autosomal dominant inheritance.

We report a family with brain calcification, predominantly in the basal ganglia, and no evident cause such as abnormal calcium or phosphorus metabolism. The proband, a 48-year-old man, had intellectual decline, parkinsonism, and mild cerebellar ataxia. He had bilateral and symmetric calcification of the basal ganglia, thalamus, dentate nucleus, cerebral cortex, subcortical white matter, and hippocampus on CT. Calcified areas showed low- or high-intensity signals on MRI T1-weighted images, and low-intensity signals on MRI T2-weighted images. Two sons and both parents, all asymptomatic, also showed calcification of the basal ganglia, suggesting an autosomal dominant inheritance. Familial idiopathic brain calcification is a rare disorder with less than 20 previously reported families. Twelve families with autosomal dominant inheritance showed a relatively homogeneous clinical picture, which may represent a distinct clinical entity. Mental deterioration, parkinsonism, and cerebellar ataxia appear in adult life and progress gradually. CT imaging, rather than MRI, is a simple and useful means to screen family members for this condition.

Effects of sumatriptan on the cerebral intraparenchymal microcirculation in the cat.

1. Sumatriptan, a 5-hydroxytryptamine (5-HT)1-like receptor agonist, is effective against the headache of migraine. The effects of sumatriptan injected via the carotid artery on the cerebral microcirculation were studied in 10 anaesthetized cats. 2. The local cerebral blood volume (CBV), mean transit time of blood (MTT) and cerebral blood flow (CBF) in the parieto-temporal cortex were measured by a photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. 3. Sumatriptan at 5 and 50 micrograms kg-1 had no significant effects on the CBV, MTT, CBF, and mean arterial blood pressure (MABP); 500 micrograms kg-1 of sumatriptan reduced the CBV, prolonged the MTT, and decreased the CBF (approximately -20%) without affecting the MABP. Sumatriptan, 5 mg kg-1, elicited transient reductions in CBV and CBF, which were attributable to the rapid and marked falls of MABP seen with this dose. 4. Thus, while a high dose of sumatriptan (500 micrograms kg-1) exhibits direct vasoconstrictor actions on the cerebral vessels, low doses of sumatriptan, within the therapeutic range, elicit no vasoconstriction. The data do not support a vasoconstrictor action of sumatriptan playing a primary role in reversing the headache of migraine.

Intraoperative radiation-therapy combined with hyperthermia for pancreatic-carcinoma.

Seventeen patients with pancreatic carcinoma were treated with intraoperative radiation therapy (IORT) combined with hyperthermia. Their treatment results were compared with those of 56 patients treated with the IORT alone (control group). The pain relief rate and the local tumor control rate of the hyperthermia group were slightly better than the control group. The survival rate of all patients was 13.7% at one year, 1.4% at two years (median, 5.0 months). The survival of the hyperthermia group was marginally better than that of the control group. Only 29% of the patients of the hyperthermia group was successfully heated, and if hyperthermia were given successfully to all patients, their prognoses would have been possibly improved.

Distinguishing patients with senile dementia of Alzheimer type and normal elderly subjects utilizing xenon CT-CBF and multivariate analysis.

Local cerebral blood flow (LCBF) was measured in 17 patients with senile dementia of Alzheimer type (SDAT) and 17 normal controls, utilizing stable xenon computed tomography (Xe CT-CBF). In patients with SDAT, LCBF values were decreased in the cerebral cortex and subcortical structures including the thalamus, basal ganglia and white matter of both hemispheres. Linear discriminant function analysis of LCBF values separated patients with SDAT from normal elderly subjects, with an error of 8.8%. Variables helpful in distinguishing SDAT patients from normal subjects were LCBF values for the frontal and temporal cortex. Multiple regression equation for predicting cognitive performance scores from LCBF values showed the best correlations with LCBF values for the frontal and occipital cortex and thalamus. Xe CT-CBF measurements provide useful information concerning diagnosis and brain function in patients with SDAT.

Swift transformation and locomotion of polymorphonuclear leukocytes and microglia as observed by VEC-DIC microscopy (video microscopy).

The detailed assembly used by us for video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy (video microscopy is first described. Employing such video microscopy, we then examined the morphological changes occurring during locomotion and activation processes of polymorphonuclear leukocytes (PMNL) and microglia at an almost electron microscopic magnification. Upon contacting the substratum, PMNL transformed into a polarized ameboid shape and crawled extending pseudopodia, as has been well documented previously. The PMNL sometimes displayed a peculiar locomotion as if they were stepping on "tiny legs", or sliding on a treadmill of cell membrane. Cultured microglia were observed to exist in 4 forms; ramified, reactive, villous, and ameboid. Microglia in the reactive form pivoted, circled and crawled on the astroglial cell layer using their transparent lamellipodia with no morphological changes in their cell body. Unlike PMNL, reactive microglia exhibited no agitated movements of their intracellular organelles, including granules and cytosol, during locomotion. Lamellipodia on the undersurface of the cell body touching the cell layer adhesively, appeared to serve as the locomotive apparatus. When activated, both floating PMNL and microglia of villous form assumed an ameboid shape within a few seconds. Microglia occasionally swam in the medium waving their lamellipodia towards a target object (e.g. zymosan A particles), remodelling to an amorphous ameboid form and covering up the target. We attempt to discuss such swift morphological changes from the standpoint of thermodynamic potential of Gibbs free energy which is stored within the cells.

Local cerebral hemodynamic changes through the angiographic stages of moyamoya disease.

In order to elucidate the cerebral hemodynamic changes that occur in Suzuki's six angiographic stages of moyamoya disease, local cerebral blood flow (LCBF) during the stable state and CO2 responsiveness of LCBF (L-CO2R: delta %LCBF/delta PaCO2) were measured by the Xenon CT-CBF method. Nineteen patients with moyamoya disease (mean age: 36.8 +/- 11.6 years) and 11 age-matched normal volunteers were studied. The LCBF during the steady state at all stages was not significantly different from that in normal volunteers. At stage 6, however, the LCBF was slightly decreased in the anterior part of the brain, resulting in loss of "hyperfrontality." On the other hand, the L-CO2R in the anterior part of the brain tended to diminish with progression through the stages. Especially in the frontal cortex, the L-CO2R at stage 5 was significantly less than that in normal volunteers (p < 0.01) or at stage 3 (p < 0.05). In conclusion, the cerebrovascular reserve in the anterior circulation became insufficient after stage 4, although the posterior circulation was well maintained. Revascularization surgery involving the anterior circulation may be crucial to prevent ischemic events.

Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model.

BACKGROUND: To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. METHODS: Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. RESULTS: IL-12/3T3 cells producing 7.2 ng/10(6) cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. CONCLUSIONS: Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers.