Intrathecal chemotherapy with ACNU in a meningeal gliomatosis rat model

1992 ◽  
Vol 77 (5) ◽  
pp. 778-782 ◽  
Author(s):  
T. Ken Yoshida ◽  
Keiji Shimizu ◽  
Athanasios Koulousakis ◽  
volker sturm
Keyword(s):  
Survival Time ◽  
Rat Model ◽  
Intrathecal Administration ◽  
Intrathecal Chemotherapy ◽  
C6 Glioma Cells ◽  
High Dose ◽  
Tumor Inoculation ◽  
Content Type ◽  
Meningeal Gliomatosis ◽  
Rat C6 Glioma

✓ Intrathecal administration of ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride) had a remarkable chemotherapeutic effect in a rat model of meningeal gliomatosis. This effect was evaluated in rats with meningeal gliomatosis induced by an intracisternal inoculation of rat C6 glioma cells. The median survival time of the rats treated with a single dose of intrathecal ACNU (1 mg/kg) on Day 1 or Day 3 after tumor inoculation was significantly prolonged by 35.7% to 42.9% or 25.0% to 28.6%, respectively, as compared with that of the control animals. Meningeal gliomatosis rat models treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg) both failed to prolong the survival time of the animals. These findings suggest that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of meningeal gliomatosis, whereas intravenous chemotherapy with a high dose of ACNU is always ineffective.

Gamma surgery for melanoma metastases in the brain

2002 ◽  
Vol 96 (3) ◽  
pp. 544-551 ◽  
Author(s):  
Vincenzo Mingione ◽  
Marcelo Oliveira ◽  
Dheerendra Prasad ◽  
Melita Steiner ◽  
Ladislau Steiner
Keyword(s):  
Brain Metastases ◽  
Survival Time ◽  
Cox Regression ◽  
Brain Lesion ◽  
High Dose ◽  
Content Type ◽  
Melanoma Metastases ◽  
The Brain ◽  
Fine Print

Object. The aim of this study was to evaluate the usefulness and limitations of gamma surgery (GS) in the treatment of brain metastases from melanoma. Methods. Imaging and clinical outcomes in 45 patients treated for 92 brain metastases from melanoma between October 1989 and October 1999 were retrospectively analyzed. Follow-up imaging studies were available in 35 patients with 66 treated lesions. Twenty-four percent of the lesions disappeared, 35% shrank, 23% remained unchanged, and 18% increased in size. No undue radiation-induced changes were observed in the surrounding brain. Clinical data were available in all patients. No deaths or neurological morbidity related to GS was observed. The median survival time, calculated using the Kaplan—Meier method, was 10.4 months from the time of GS. In both univariate and multivariate Cox regression analyses, a single brain lesion and lack of visceral metastases were statistically predictive of a better prognosis. Six of eight patients with solitary metastasis (that is, a single brain metastasis with no primary visceral tumor) were still alive at the close of the study, none of them with disease progression, with a follow-up period ranging between 14 and 82 months. Sixteen patients in this series received adjunctive whole-brain radiation therapy, which had no impact on their survival time or local and distant control of the brain disease. Conclusions. Gamma surgery is effective in treating melanoma metastases in the brain. It appears that the radiobiology of a single high dose overcomes the radioresistance barrier, yielding better results than fractionated radiation.

Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas

1999 ◽  
Vol 91 (2) ◽  
pp. 221-230 ◽  
Author(s):  
Shoju Hiraga ◽  
Norio Arita ◽  
Takanori Ohnishi ◽  
Eiji Kohmura ◽  
Kazumi Yamamoto ◽  
...  
Keyword(s):  
Survival Time ◽  
Tumor Volume ◽  
Tumor Response ◽  
Infusion Therapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Rapid Infusion ◽  
Content Type ◽  
Dose Methotrexate ◽  
Fine Print

Object. Twenty-nine nonimmunocompromised patients with primary central nervous system (CNS) lymphoma were treated with high-dose methotrexate (MTX) therapy followed by irradiation. The authors investigated the correlation of infusion schedules with MTX penetration into cerebrospinal fluid (CSF), tumor response, and survival to develop a regimen that would lead to better clinical results.Methods. In this study, 100 mg/kg MTX was administered on either a rapid (3-hour) or regular (6-hour) infusion schedule for two or three cycles. Of 28 assessable patients, a complete or partial response was achieved in 15 (93.8%) of 16 who received rapid and in seven (58.3%) of 12 who received regular infusion therapy (p = 0.034). Rapid infusion significantly increased levels of MTX in the CSF (p < 0.001) and resulted in significant tumor volume reduction (p < 0.001). The mean tumor volume after the first, second, and third cycle of rapid infusion therapy was reduced to 34%, 14%, and 9%, respectively, of the initial volume, whereas the corresponding values were 54%, 42%, and 37% for regular infusion. The reduction between the second and third cycle was small and not significant for either schedule. Despite the longer median survival time in patients who underwent rapid MTX infusion and irradiation (> 60 compared with 20 months), the difference in survival was not significant (p = 0.147) because of the small number of patients enrolled. The median survival time was 39.3 months for all assessable patients who received high-dose MTX and radiation therapy, and the median relapse-free survival time was 35.2 months.Conclusions. Rapid infusion enhanced both MTX penetration into the CSF and tumor response and may improve patient survival. Administration of three or more cycles of therapy should be carefully weighed in terms of cytoreductive benefits.

Inhibitory effect of antisense epidermal growth factor receptor RNA on the proliferation of rat C6 glioma cells in vitro and in vivo

2000 ◽  
Vol 92 (1) ◽  
pp. 132-139 ◽  
Author(s):  
Peiyu Pu ◽  
Xuwen Liu ◽  
Aixue Liu ◽  
Jianling Cui ◽  
Yunting Zhang
Keyword(s):  
Survival Time ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
C6 Cells ◽  
Content Type ◽  
Proliferation Activity ◽  
Fine Print

Object. The goal of this study was to evaluate the effect of antisense epidermal growth factor receptor (EGFR) RNA on the growth of rat glioma cells in vitro and in vivo and to determine the feasibility of targeting the EGFR gene for gene therapy in gliomas.Methods. Antisense EGFR complementary (c)DNA was transfected into C6 glioma cells by using lipofectamine. In vitro studies, Southern and Northern blot analyses, in situ hybridization, and immunohistochemical staining were designed to examine the integration and expression of antisense EGFR constructs. The 3′(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay and the average number of argyrophilic nuclear organizer regions (Ag-NORs) were used to evaluate cell proliferation, whereas the terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method and microscopy were used to observe cell apoptosis. As part of the in vivo studies, parental C6 cells and C6 cells transfected with EGFR antisense cDNA were implanted stereotactically into the right caudate nucleus of Wistar rats (C6-injected animals and transfected C6-injected animals). Rats with well-established cerebral C6 glioma foci were treated intratumorally with either antisense EGFR cDNA or empty-vector DNA by using lipofectamine (treated-C6 and control treated group). The general behavior and survival of the rats, findings on magnetic resonance images of their brains, histopathological changes, proliferation activity, and apoptosis of the cerebral gliomas in each group of rats were examined.Exogenous antisense EGFR cDNA was integrated into the genome of C6 cells and expressed. In clones with a high expression of the antisense construct, there was a dramatic decrease in endogenous EGFR messenger RNA and protein levels, reduced proliferation activity, and induction of apoptosis in vitro. The mean survival time of rats injected with C6 cells was 17.3 days. The mean survival time of rats injected with C6 cells followed by treatment with empty vector in lipofectamine was 15.4 days. Survival time was significantly prolonged in 100% of the rats injected with antisense-transfected C6 cells and in two thirds of the rats injected with C6 cells followed by antisense EGFR cDNA. Magnetic resonance imaging revealed distinct cerebral tumor foci in C6-injected rats and in control rats of the treated group, but none were found in the rats injected with transfected C6 cells. Furthermore, tumor foci disappeared completely in C6-injected rats treated with antisense EGFR cDNA. The cerebral gliomas of the rats treated by injection of antisense EGFR RNA were characterized by reduced proliferation activity and the induction of apoptosis.Conclusions. The results of this study indicate that EGFR plays an important role in the genesis of malignant gliomas. It may, therefore, be an effective target of antisense gene therapy in patients with gliomas.

Alteration of blood-CSF barrier by tumor invasion into the meninges

1981 ◽  
Vol 55 (3) ◽  
pp. 445-449 ◽  
Author(s):  
Yukitaka Ushio ◽  
Keiji Shimizu ◽  
Yasuo Aragaki ◽  
Norio Arita ◽  
Toru Hayakawa ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Tumor Invasion ◽  
Early Stage ◽  
Tumor Inoculation ◽  
Maximum Increase ◽  
Walker 256 Carcinosarcoma ◽  
Content Type ◽  
Walker 256 ◽  
Prevent Tumor Growth

✓ Cyclophosphamide and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) were found to have an equivalent cytostatic effect in rats with subcutaneous transplants of Walker 256 carcinosarcoma. Rats with meningeal carcinomatosis received a single intravenous dose of cyclophosphamide (30 mg/kg) or ACNU (15 mg/kg) at various times after intracisternal inoculation of 1 × 104 Walker 256 carcinosarcoma cells. Cyclophosphamide, administered 1 day after tumor inoculation, failed to prevent tumor growth in the subarachnoid space. The survival time of these rats was prolonged only 10% to 14% compared to the controls, while ACNU produced a maximum increased survival time of 180%. If administered 2, 3, 4, and 5 days after tumor inoculation, both drugs were effective; cyclophosphamide yielded a maximum increase in median survival time of 109%, 94%, 90%, and 52%, and ACNU 127%, 139%, 240%, and 100%, respectively. These results indicate that the blood-cerebrospinal fluid (CSF) barrier was circumvented in the early stage of subarachnoid tumor growth, although some areas remained where the infiltrating tumor cells were protected from systemically administered drugs by the intact barrier.

Dual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy

1998 ◽  
Vol 89 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Richard B. Schwartz ◽  
B. Leonard Holman ◽  
Joseph F. Polak ◽  
Basem M. Garada ◽  
Marc S. Schwartz ◽  
...  
Keyword(s):  
Survival Rate ◽  
Glioblastoma Multiforme ◽  
Single Photon ◽  
Photon Emission ◽  
High Dose ◽  
Term Survival ◽  
Content Type ◽  
Dual Isotope ◽  
Fine Print

Object. The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. Methods. Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan—Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201T1 ratio < 2 and 99mTc-HMPAO ratio of ≥ 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio ≥ 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01); however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). Conclusions. Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.

Gamma knife radiosurgery in patients with advanced breast cancer undergoing bone marrow transplant

2002 ◽  
Vol 97 ◽  
pp. 663-665 ◽  
Author(s):  
Kenneth J. Levin ◽  
Emad F. Youssef ◽  
Andrew E. Sloan ◽  
Rajiv Patel ◽  
Rana K. Zabad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
High Dose Chemotherapy ◽  
Advanced Breast ◽  
High Dose ◽  
Initial Management ◽  
Content Type ◽  
Fine Print

Object. Recent studies have suggested a high incidence of cognitive deficits in patients undergoing high-dose chemotherapy, which appears to be dose related. Whole-brain radiotherapy (WBRT) has previously been associated with cognitive impairment. The authors attempted to use gamma knife radiosurgery (GKS) to delay or avoid WBRT in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT) in whom brain metastases were diagnosed. Methods. A retrospective review of our experience from 1996 to 2001 was performed to identify patients who underwent HDC/ABMT for advanced breast cancer and brain metastasis. They were able to conduct GKS as initial management to avoid or delay WBRT in 12 patients following HDC/ABMT. All patients were women. The median age was 48 years (range 30–58 years). The Karnofsky Performance Scale score was 70 (range 60–90). All lesions were treated with a median prescription dose of 17 Gy (range 15–18 Gy) prescribed to the 50% isodose. Median survival was 11.5 months. Five patients (42%) had no evidence of central nervous system disease progression and no further treatment was given. Four patients were retreated with GKS and three of them eventually received WBRT as well. Two patients were treated with WBRT as the primary salvage therapy. The median time to retreatment with WBRT was 8 months after the initial GKS. Conclusions. Gamma knife radiosurgery can be effectively used for the initial management of brain metastases to avoid or delay WBRT in patients treated previously with HDC, with acceptable survival and preserved cognitive function.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

Presence and significance of NK cells in glioblastomas

1989 ◽  
Vol 70 (5) ◽  
pp. 728-731 ◽  
Author(s):  
Jesús Vaquero ◽  
Santiago Coca ◽  
Santiago Oya ◽  
Roberto Martínez ◽  
Josefa Ramiro ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Nk Cells ◽  
Survival Time ◽  
Tumor Cells ◽  
Lymphocytic Infiltration ◽  
Surface Marker ◽  
Content Type ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining ◽  
Fine Print

✓ A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence of these cells in a series of 25 glioblastomas. In 40% of the tumors, IOT-10-positive NK cells were found in small numbers scattered among the tumor cells. The presence of IOT-10-positive NK cells was not related to the degree of lymphocytic infiltration in the tumor as demonstrated by hematoxylin and eosin staining, nor did it appear to influence the survival time of the patients studied.

scholarly journals Impact of calcitriol and an AKT inhibitor, AT7867, on survival of rat C6 glioma cells

2021 ◽  
Vol 35 (1) ◽  
pp. 730-738
Author(s):  
Ozlem Kucukhuseyin ◽  
Aris Cakiris ◽  
Mehmet Tolgahan Hakan ◽  
Cem Horozoglu ◽  
Erdem Tuzun ◽  
...  
Keyword(s):  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Akt Inhibitor ◽  
Rat C6 Glioma
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