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Biomedical subjects

Z Ram

Publications and source records attributed to Z Ram.

At least 19 recordsLinked to original sources
PubMed1999

Application of transcranial doppler ultrasonography for the diagnosis of brain death.

OBJECTIVE: To determine the clinical validity of transcranial Doppler ultrasonographic (TCD) signs of total cerebral circulatory arrest for confirmation of brain death and to define the test protocol. DESIGN: Study of a diagnostic test. SETTING: General and neurosurgery intensive care units. PATIENTS: 137 patients in a coma (Glasgow Coma Score 3-5), caused by various pathological conditions, observed from January 1992 to July 1998. 84 patients met the clinical criteria of brain death; 43 patients out of 137 received sedative drug therapy and 31 of these developed brain death. RESULTS: Total cerebral circulatory arrest was demonstrated by TCD in 81 patients. All of them proved to be brain dead according to subsequent clinical examination In 29 of 31 patients who had received sedative drug therapy TCD examination showed total cerebral circulatory arrest 12-48 h before the formal confirmation of the diagnosis. In 1 out of 84 clinically brain dead patients a false negative result was obtained. In 2 of 84 cases, no clear signals from intracranial vessels were obtainable. Fifty-three patients who did not meet the clinical criteria for brain death showed no TCD signs of total cerebral circulatory arrest. The specificity of the TCD test for confirmation of brain death was 100 % and the sensitivity 96.5 %. CONCLUSIONS: In agreement with previously published data, we conclude that TCD ultrasonography is a highly specific and sensitive confirmatory test and should be included as an additional test in the protocol for the assessment of brain death.

Adolescent↗
PubMed1998

[Propofol anesthesia for craniotomy in patients who are awake].

During craniotomy, the patient's cooperation is needed during procedures in which continuous neurological examination and mapping of crucial regions close to the area to be resected area are required. We report our experience in 9 patients who underwent such procedures under intravenous propofol as the main sedating agent. This short-acting hypnotic was administered prior to and during the painful stages of the procedure. Patients were fully asleep when the skull was opened and the dural flap raised or excised. During the rest of the operation patients were lightly sedated but remained responsive and cooperative. This enabled precise intra-operative mapping of the brain and surgery-related neurological deficits were avoided. Respiratory depression or hemodynamic compromise were not encountered. All patients were comfortable during the operation and there were no additional neurological deficits after operation. We believe that propofol should be the main sedating agent used for these procedures.

Aged↗
PubMed1997

Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells.

Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase (HSV-TK) gene induces regression of experimental brain tumors in rodents after ganciclovir (GCV) administration. We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors. Antitumor activity was detected in five of the smaller tumors (1.4 +/- 0.5 ml). In situ hybridization for HSV-TK demonstrated survival of vector-producing cells (VPCs) at 7 days but indicated limited gene transfer to tumors, suggesting that indirect, "bystander," mechanisms provide local antitumor activity in human tumors. However, the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach.

Adult↗
PubMed1997

Mechanism of 'bystander effect' killing in the herpes simplex thymidine kinase gene therapy model of cancer treatment.

'Bystander' killing of adjacent wild-type tumor cells was seen when tumors transduced with the herpes thymidine kinase gene were treated with the antiviral agent ganciclovir (GCV). Some tumors were 'bystander-sensitive' while others were 'bystander-resistant'. Mixtures of different 'sensitive' tumor lines showed cross-transfer of bystander killing, while in mixtures of 'resistant' with 'sensitive' tumors, the resistant phenotype was predominant. Using 3H-GCV with 'sensitive' mixtures, phosphorylated 3H-GCV was found in both herpes thymidine kinase transduced and unmodified cells, while 'resistant' cell combinations showed little or no transfer of phosphorylated GCV between cells. The capacity of intracellularly produced nucleotide toxin to spread from cell to cell within a tumor mass effectively amplifies the apparent efficiency of gene transfer in the tumor and makes feasible the use of this system for therapy of localized cancer.

Adenocarcinoma↗
PubMed1997

Transiently increased basilar artery flow velocity following severe head injury: a time course transcranial Doppler study.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography has been used to study changes in cerebral hemodynamics following head injury. However, most studies evaluated the anterior circulation and little information exists on transcranial Doppler of the vertebrobasilar arteries after head injury. METHODS: Thirty-two patients with a Glasgow Coma Scale (GCS) score between 4-8 and 11 patients with a GCS score between 9-14 were studied using transcranial Doppler ultrasonography for the first 10 days after injury. Daily variations in the mean blood flow velocities of all major cerebral arteries were recorded. RESULTS: In patients with GCS score between 4-8, the mean blood flow velocities in the middle cerebral and basilar arteries gradually increased beginning on day 2 postinjury and peaked on the 4th-5th day after injury. Those changes were more prominent, and appeared earlier, in the basilar artery. The ratio between the mean flow velocities of the middle cerebral artery and the basilar artery during the first 4 days was significantly lower than in normal controls, indicating a particular increase of flow velocity in the basilar artery. Nineteen out of 32 patients (60%) with severe head injury showed mean blood flow velocity increased over 75 cm/sec in the basilar artery. Mean blood flow velocity >90 cm/sec in the basilar artery, compatible with vasospasm, was observed in 12 of 32 patients (37%). Spasm in the middle cerebral artery was observed in 12 (37%) of patients; 10 of them also had evidence of basilar artery spasm. On the whole, 14 of 32 (43%) patients had evidence of spasm either in the middle cerebral or basilar arteries or in both. In 5 of 11 patients (50%) with moderate head injury (GCS score 9-14), blood flow velocity in the basilar artery greater than 75 cm/sec was observed, but in only two of them it reached the values over 90 cm/sec. Vasospasm in the middle cerebral artery was noted in one patient. CONCLUSIONS: A significant number of patients develop increased flow velocities compatible with vasospasm in the basilar artery after severe head injury. This phenomenon may represent an additional factor that contributes to the poor outcome of severely head-injured patients.

Adolescent↗
PubMed1997

Antiproliferative effects of cyclopentenyl cytosine (NSC 375575) in human glioblastoma cells.

Cyclopentenyl cytosine (CPEC) exerts an antiproliferative effect against a wide variety of human and murine tumor lines, including a panel of human gliosarcoma and astrocytoma lines. This effect is produced primarily by the 5'-triphosphate metabolite CPEC-TP, an inhibitor of cytidine-5'-triphosphate (CTP) synthase (EC 6.3.4.2). Because previous studies with human glioma cell lines utilized cells in long-term tissue culture, we have undertaken to determine whether the activity of CPEC in such model systems is also demonstrable in freshly excised human glioblastoma cells. Glioma cells obtained at surgery and in log phase growth were exposed to the drug at levels ranging from 0.01 to 1 microM for 24 h, and CPEC-TP and CTP levels were determined by HPLC. Dose-dependent accumulation of CPEC-TP was accompanied by a concomitant decrease in CTP pools, with 50% depletion of the latter being achieved at a CPEC level of ca. 0.1 microM. Human glioma cell proliferation was inhibited 50% by 24-h exposure to 0.07 microM CPEC. Postexposure decay of CPEC-TP was slow, with a half-time of 30 h. DNA cytometry showed a dose-dependent shift in cell cycle distribution, with an accumulation of cells in S-phase. The pharmacological effects of CPEC on freshly excised glioblastoma cells are quantitatively similar to those seen in a range of established tissue culture lines, including human glioma, colon carcinoma, and MOLT-4 lymphoblasts, supporting the recommendation that the drug may be advantageous for the treatment of human glioblastoma.

Adult↗
PubMed1995

In situ cyclopentenyl cytosine infusion for the treatment of experimental brain tumors.

Cyclopentenylcytosine (CPEC; NSC 375575) is a pyrimidine nucleoside analogue that has potent antitumor effects when tested in vitro and also when tested in experimental tumors outside the central nervous system. CPEC exerts its antiproliferative effect through inhibition of CTP synthetase and consequent depletion of CTP and dCTP pools required for cell replication. Due to its poor penetration of the bloodbrain barrier, CPEC has failed to demonstrate therapeutic efficacy in experimental brain tumors after systemic administration. We therefore examined the in vivo activation, distribution, and antitumor effect of CPEC after long-term regional infusion of the drug directly into experimental brain tumors in rats. HPLC analysis of CPEC incubated with homogenized human brain and brain tumor tissue showed minimal degradation of the drug over 24 h. Analysis of rat cerebral 9L gliosarcoma infused with tritium-labeled CPEC demonstrated intratumoral accumulation of the active metabolite CPEC-triphosphate and concomitant depletion of CTP to a much greater extent in tumor tissue than in the adjacent brain. Tumor tissue UTP also decreased, but no significant effects on other ribonucleoside triphosphates were detected. Only trace amounts (< 1%) of CPEC and its metabolites reached peripheral sites, including the liver and kidneys, after intratumoral infusion. Rats treated with continuous intratumoral infusion of CPEC for 4 weeks using s.c. implanted osmotic pumps survived significantly longer than control rats receiving intratumoral saline or i.p. CPEC (P < 0.0001). Long-term intratumoral infusion of CPEC was not associated with any detectable toxicity. Our results support the feasibility of using intratumoral administration of CPEC as a regional therapy for malignant brain tumors.

Animals↗
PubMed1995

Adenovirally mediated gene transfer into experimental solid brain tumors and leptomeningeal cancer cells.

Among the appealing features of adenoviruses as vectors for transfer of genes into the central nervous system (CNS) are that they are not neurotoxic, they can accommodate the insertion of several large genes, they are not associated with the hazards of insertional mutagenesis, and they can be concentrated to a high-titer preparation. The authors evaluated the feasibility of using adenovirally mediated gene transfer into cultured human glioma cells and in rat models of solid brain tumors and meningeal cancer. Replication-deficient adenoviral vector particles carrying a nuclear-localizing lacZ gene were injected into established 9L cerebral gliomas in Fischer rats. In addition, the adenoviral vector was injected into the subarachnoid space, either simultaneously with intrathecal tumor inoculation or after establishing leptomeningeal cancer. The brains and spinal cords were removed at various intervals for histochemical evaluation for beta-galactosidase activity using X-Gal staining. Additional rats received a stereotactic intracerebral injection of the vector into normal brain. No clinical abnormalities were observed in the injected rats. Injection of the adenoviral vector into normal brain resulted in diffuse transduction of astrocytes, microglia, neurons, and endothelial cells at the injection site. Injection of a high-concentration vector preparation into cerebral gliomas resulted in effective tumor transduction. Intrathecal injection of the vector in rats with meningeal cancer resulted in transduction of the infiltrating tumor in the subarachnoid space when injections were given simultaneously with, or 7 days after, tumor inoculation. Transduction rates of both solid and leptomeningeal tumors correlated with the number of injected particles. These results suggest that adenoviral vectors can efficiently transduce solid brain tumors and that the vectors survive in the cerebrospinal fluid for a sufficient period of time to allow leptomeningeal tumor transduction. Adenoviral vector should be evaluated for its potential use in therapeutic gene transfer approaches in malignancies of the CNS.

Adenoviridae↗
PubMed1995

Intraoperative ultrasound-directed resection of pituitary tumors.

Microadenomas of the pituitary vary in size, particularly those related to Cushing's disease. They are often not visualized on preoperative magnetic resonance (MR) imaging and may be difficult to find during surgical exploration of the pituitary. To enhance intraoperative localization of pituitary adenomas, we assessed the feasibility of using ultrasound to detect and localize pituitary tumors. Intraoperative ultrasound (IS) in the axial and sagittal planes was performed with an Intrascan system using a 12-MHz mechanically oscillating, end-firing transducer. Interpretation of the scans was performed by two individuals, who were usually blinded to the results of preoperative MR imaging or petrosal sinus sampling. Twenty-eight patients were examined. Eighteen of these patients had microadenomas (1.5-7 mm), all with Cushing's disease; nine had macroadenomas (10-20 mm), three of which were adrenocorticotropic hormone-secreting, three growth hormone-secreting, two thyroid-stimulating hormone-secreting, and one nonfunctioning; and one patient had an intrasellar craniopharyngioma. Normal sellar and parasellar structures, such as intrapituitary cysts, the intracavernous carotid arteries, and the diaphragma sella were easily visualized. Twenty-three of the 28 tumors, including 13 of the 18 microadenomas, were detected on IS (82% sensitivity). Tumors were seen as hyperechoic masses in 19 patients, mixed echogenicity in three, and isoechoic in one. In most macroadenomas IS allowed visualization of the interface between the tumor and the normal pituitary gland. These results indicate the potential of IS to aid the intraoperative localization and definition of pituitary tumors.

Adenoma↗
PubMed1995

Toxicity studies and distribution dynamics of retroviral vectors following intrathecal administration of retroviral vector-producer cells.

The use of intrathecal, retroviral-mediated transfer of the herpes simplex thymidine kinase (HStk) gene and subsequent ganciclovir (GCV) administration has recently been shown to improve survival in a rat model of leptomeningeal carcinomatosis. Clinical application of this approach is attractive because access to the cerebrospinal fluid (CSF) space is relatively noninvasive and distribution of producer cells and vectors may be facilitated by circulation of CSF, overcoming distribution problems inherent in solid tumors. However, meningeal inflammation, transduction and injury to normal CNS tissue, proliferation of the xenogeneic producer cells in the subarachnoid space, immune-mediated injury, and development of hydrocephalus are possible complications of intraventricular or intrathecal administration of vector-producer cells. In addition, the dynamics of producer cell and vector distribution in the CSF are unknown. To address these issues, we evaluated the safety of this approach for gene delivery and assessed the dynamics of distribution of producer cells and retroviral vectors in rats and non-human primates. In rats, transduction of normal central nervous system (CNS) structures surrounding the subarachnoid space was evaluated after intrathecal and intraventricular injections of beta-galactosidase and HStk vector-producer cells, with and without GCV. In primates, beta-galactosidase and HStk vector-producer cells were injected intraventricularly and GCV was administered either intrathecally or intravenously. Toxicity was evaluated by neurologic examination, serial gadolinium-enhanced MRI scans of the brain, and blood and CSF profiles. A subgroup of monkeys received repeated intraventricular injection of vector-producer cells and intravenous GCV. The titer of retroviral-vector was measured in cisternal and lumbar CSF samples after repeated producer cell injection.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1994

Growth inhibition, tumor maturation, and extended survival in experimental brain tumors in rats treated with phenylacetate.

Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further.

Animals↗
PubMed1994

Intrathecal gene therapy for malignant leptomeningeal neoplasia.

In meningeal carcinomatosis, retroviral vector-producer cells can be introduced into the thecal sac and circulate in the cerebrospinal fluid to reach malignant tumor cells in the leptomeninges, release vector particles, and selectively infect and transfer a gene of interest to these cells. Gene transfer experiments with the lacZ gene and in vitro retroviral titer measurements showed that retroviral vectors can survive in the cerebrospinal fluid, retain their infectivity, and successfully transduce tumor cells. To examine the potential of intrathecal gene therapy, we evaluated the antitumor efficacy of in situ transduction with the herpes simplex-thymidine kinase gene followed by ganciclovir therapy in a rat model of leptomeningeal neoplasia. Fischer rats were inoculated via a subarachnoid catheter implanted at the upper thoracic level, and thymidine kinase vector-producer cells were injected into the subarachnoid space the day of tumor inoculation. Seven days later, rats received ganciclovir for 14 days by daily i.p. injections (30 mg/kg/ml) or intrathecal injections (25 micrograms/kg or 600 micrograms/kg) for 14 days. To evaluate possible enhancement of tumor eradication by the ability of helper virus to package the vector in the cells and further extend gene transfer, additional rats received thymidine kinase vector-producer cells that had been previously coinfected with a replication-competent retrovirus (4070A). In all groups, control rats received i.p. or intrathecal saline injections. Ganciclovir administration i.p. resulted in significant prolongation of survival in rats given injections of thymidine kinase vector-producer cells. Injection of producer cells coinfected with the 4070A retrovirus did not improve antitumor efficacy. Intrathecal administration of ganciclovir (low and high doses) did not extend survival; histological examination of the spinal cords showed elimination of the infiltrative tumor in the leptomeninges, but residual tumor mass was present at the inoculation site, consistent with limited penetration of topical ganciclovir into the tumor. These results support the potential application of gene therapy using the thymidine kinase/ganciclovir approach for treatment of meningeal carcinomatosis.

3T3 Cells↗
PubMed1994

Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria.

Phenylacetate, a deaminated metabolite of phenylalanine, has been implicated in damage to immature brain in phenylketonuria. Because primary brain tumors are highly reminiscent of the immature central nervous system, these neoplasms should be equally vulnerable. We show here that sodium phenylacetate can induce cytostasis and reversal of malignant properties of cultured human glioblastoma cells, when used at pharmacological concentrations that are well tolerated by children and adults. Treated tumor cells exhibited biochemical alterations similar to those observed in phenylketonuria-like conditions, including selective decline in de novo cholesterol synthesis from mevalonate. Because gliomas, but not mature normal brain cells, are highly dependent on mevalonate for production of sterols and isoprenoids vital for cell growth, sodium phenylacetate would be expected to affect tumor growth in vivo while sparing normal tissues. Systemic treatment of rats bearing intracranial gliomas resulted in significant tumor suppression with no apparent toxicity to the host. The data indicate that phenylacetate, acting through inhibition of protein prenylation and other mechanisms, may offer a safe and effective novel approach to treatment of malignant gliomas and perhaps other neoplasms as well.

Animals↗
PubMed1994

Intraoperative US of the pituitary gland. Work in progress.

PURPOSE: To evaluate the use of ultrasound (US) of the pituitary gland during transsphenoidal surgery as a means of detecting microadenomas in patients with Cushing disease. MATERIALS AND METHODS: Thirteen patients with Cushing disease and one with acromegaly underwent US during transsphenoidal surgery. Mechanically oscillating transducers (10 MHz [n = 8] or 15 MHz [n = 6]) mounted on a 15-cm-long probe were used. RESULTS: Seven adenomas were definitely visualized, two were poorly seen, and four were overlooked. Small tumors (< 5 mm in diameter) tended to be hypoechoic; larger ones, hyperechoic. All four overlooked adenomas were imaged with the 15-MHz transducer. The cavernous sinuses and internal carotid arteries could be seen, but minimal invasion of the medial wall of the cavernous sinus could not. CONCLUSION: Pituitary microadenomas can be detected with transsphenoidal US; however, evaluation of larger series with instrumentation developed specifically for transsphenoidal application will be necessary to determine the ultimate value of this technique.

Acromegaly↗
PubMed1994

Early repeat surgery for persistent Cushing's disease.

The potential efficacy of early repeat transsphenoidal surgery for persistent Cushing's disease has not previously been examined. On 222 patients with no prior pituitary treatment and a preoperative diagnosis of Cushing's disease, 29 (13%) remained hypercortisolemic after an initial transsphenoidal pituitary exploration. Seventeen of these 29 patients underwent further surgery 7 to 46 days after the initial transsphenoidal approach in order to completely excise suspected residual tumor. Patients were followed for 4 to 84 months (mean +/- standard deviation, 34 +/- 25 months) to document sustained remission or recurrence of Cushing's disease (a urine free cortisol level > 90 micrograms/day was considered evidence of recurrence). Of the 17 patients with repeat surgery, 12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5 micrograms/dl); however, in three of these 12, hypercortisolism recurred 5, 12, and 24 months later. In 14 patients a lesion that appeared to be a tumor was identified during the initial procedure or on histological examination. Of these, 12 had immediate resolution of hypercortisolism and nine are still in remission. Three patients, in whom no adenoma could be identified during the initial surgery or an examination of the partial hypophysectomy specimen from the initial surgery, had persistent Cushing's syndrome after the second operation. Seven (41%) of the 17 patients developed hypopituitarism requiring treatment with thyroid hormone, gonadal steroid, or vasopressin replacement. The low incidence of identification of an adenoma on computerized tomography or magnetic resonance images (three of 17 patients), the failure to find a corticotrophic adenoma during the initial surgery (10 of 17 patients), and the failure of these 17 patients to respond to the initial transsphenoidal surgery suggest that they may comprise a subset of patients who are more difficult to treat successfully with surgery than most patients with Cushing's disease. Despite that, early reoperation induced immediate remission of hypercortisolism in 71% of cases, but did so at the expense of a high risk of hypopituitarism. However, since the alternative treatments (such as radiation therapy, long-term drug therapy, or bilateral adrenalectomy) also have potential adverse effects, early reoperation deserves consideration for the management of persistent Cushing's disease, especially when an adrenocorticotrophic hormone-secreting adenoma was partially excised during the first surgery.

Adult↗
PubMed1994

In vivo transfer of the human interleukin-2 gene: negative tumoricidal results in experimental brain tumors.

The authors have recently shown the feasibility of eradicating brain tumors using in vivo retroviral-mediated transduction of tumors with the herpes simplex thymidine kinase (HStk) gene and ganciclovir therapy. However, thymidine kinase-transduced subcutaneous tumors in immunocompromised (athymic) mice were less responsive to this therapy than in immunocompetent animals, suggesting a role of the immune system in the process of tumor eradication. Broad suppression of humoral and cell-mediated immunity is found in patients with malignant gliomas. Interleukin-2 (IL-2) production and IL-2 receptor expression are decreased in gliomas patients. These findings and the proposed association between lymphocytic infiltration of brain tumors and survival suggest that immune response modifiers may be useful in treating glioma patients. To evaluate the role of local cytokine expression by tumor cells, alone or combined with HStk gene transfer and ganciclovir therapy, the authors investigated the efficacy of tumor (9L gliosarcoma) eradication in Fischer rats by in vitro and in vivo tumor transduction with the IL-2 gene alone or with a combined vector carrying both the HStk and IL-2 genes. Tumors injected with HStk vector-producer cells alone, with or without ganciclovir, and rats inoculated in the brain and subcutaneously with 9L cells that had previously been transduced in vitro served as controls. Murine vector-producer cells (3 x 10(6)/50 microliters) were injected into the brain tumors 7 days after tumor inoculation. Ganciclovir (15 mg/kg) was administered intraperitoneally twice daily for 10 days to animals that received HStk with or without IL-2 vector-producer cells, starting 5 days after producer-cell injection. The experiment was repeated with continuous daily treatment of all rats with oral dexamethasone (0.5 mg/kg). Rats were sacrificed 21 days after tumor inoculation, and the brains were removed for histological and immunohistochemical analysis for IL-2. Within each experimental group, tumors were found in a similar proportion in the dexamethasone-treated and untreated rats. Large brain tumors developed in all 10 rats that had been inoculated with 9L cells which had been pretransduced in vitro with the IL-2 gene, whereas only three of eight rats receiving subcutaneous inoculation of similar cells developed palpable tumors. No enhancement of tumor eradication was observed by adding the IL-2 gene in the HStk vector construct compared to the use of the vector with HStk alone. Lymphocytic infiltration was absent in all dexamethasone-treated rats but was observed in all treatment groups not receiving steroids.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗