Chemotherapeutic trials on human malignant astrocytomas in organ culture

1977 ◽  
Vol 46 (3) ◽  
pp. 320-327 ◽  
Author(s):  
Ruben J. Saez ◽  
R. Jean Campbell ◽  
Edward R. Laws
Keyword(s):  
Organ Culture ◽  
Malignant Gliomas ◽  
Three Dimensional ◽  
Drug Effects ◽  
Porous Matrix ◽  
Pharmacological Management ◽  
Content Type ◽  
Malignant Astrocytomas ◽  
The Matrix

✓ A technique of organ culture based on a three-dimensional porous matrix was employed for chemotherapeutic trials on human malignant astrocytomas. This method allows neoplasms to retain the morphological identity and the histological characteristics they possess in vivo. Success in culture was greatest with high-grade astrocytomas, the majority of which showed definite infiltration of the matrix. Lowgrade tumors, if viable, did not display active penetration. Drug trials on eight malignant astrocytomas included BCNU, methyl CCNU, VP 16–213, and Solu-Medrol. Cyanide and luciferase were used as experimental metabolic toxins. Evidence of cytotoxicity was assessed qualitatively by histological changes on microscopic preparations of treated and control cultures. Microfluorometric determinations of reduced nicotinamide adenine dinucleotide (NADH) were applied to these trials in an effort to detect a quantitative biochemical index of drug effects. A variable rise in mean NADH levels above controls was recorded from the majority of treated cultures although correlation with microscopic changes was inconsistent. Because of its potential merits, organ culture may be a valuable tool for further work on pharmacological management of malignant gliomas.

Administration of interleukin-12 and -18 enhancing the antitumor immunity of genetically modified dendritic cells that had been pulsed with Semliki Forest virus—mediated tumor complementary DNA

2002 ◽  
Vol 97 (5) ◽  
pp. 1184-1190 ◽  
Author(s):  
Ryuya Yamanaka ◽  
Naoki Yajima ◽  
Naoto Tsuchiya ◽  
Junpei Honma ◽  
Ryuichi Tanaka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antitumor Immunity ◽  
Semliki Forest Virus ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Antitumor Effects ◽  
Content Type ◽  
Immunogene Therapy ◽  
Fine Print

Object. Immunogene therapy for malignant gliomas was further investigated in this study to improve its therapeutic efficacy. Methods. Dendritic cells (DCs) were isolated from bone marrow and pulsed with phosphate-buffered saline or Semliki Forest virus (SFV)—mediated 203 glioma complementary (c)DNA with or without systemic administration of interleukin (IL)-12 and IL-18 to treat mice bearing the 203 glioma. To study the immune mechanisms involved in tumor regression, the authors investigated tumor growth of an implanted 203 glioma model in T cell subset—depleted mice and in interferon (IFN) γ—neutralized mice. To examine the protective immunity produced by tumor inoculation, a repeated challenge of 203 glioma cells was given by injecting the cells into the left thighs of surviving mice and the growth of these cells was monitored. The authors demonstrated that the combined administration of SFV-cDNA, IL-12, and IL-18 produced significant antitumor effects against the growth of murine glioma cells in vivo and also can induce specific antitumor immunity. The synergic effects of the combination of SFV-cDNA, IL-12, and IL-18 in vivo were also observed to coincide with markedly augmented IFNγ production. The antitumor effects of this combined therapy are mediated by CD4+ and CD8+ T cells and by NK cells. These results indicate that the use of IL-18 and IL-12 in DC-based immunotherapy for malignant glioma is beneficial. Conclusions. Immunogene therapy combined with DC therapy, IL-12, and IL-18 may be an excellent candidate in the development of a new treatment protocol. The self-replicating SFV system may therefore provide a novel approach for the treatment of malignant gliomas.

Service quality function deployment by the C-shaped QFD 3D matrix

2018 ◽  
Vol 25 (9) ◽  
pp. 3386-3405 ◽  
Author(s):  
Maryam Hassani ◽  
Arash Shahin ◽  
Manouchehr Kheradmandnia
Keyword(s):  
Quality Function Deployment ◽  
Design Methodology ◽  
Three Dimensional ◽  
Two Dimensional ◽  
Customer Requirements ◽  
Content Type ◽  
Process Characteristics ◽  
The Matrix ◽  
3D Matrix ◽  
Simultaneous Comparison

Purpose The purpose of this paper is to examine the application of C-shaped QFD 3D Matrix in comparing process characteristics (PC), performance aspects (PA) and customer requirements, simultaneously and to prioritize the first two sets, respectively. Design/methodology/approach A three dimensional matrix has been developed with three sets of PC, PA and customers’ requirements and C-shaped matrix has been applied for simultaneous comparison of the dimensions and prioritization of the subsets of PC and PA. The proposed approach has been examined in a post bank. Findings Findings confirm the possibility of simultaneous comparison and prioritization of the three sets of dimensions of this study in post bank services. In addition, “growth and learning” and “bilateral relationship with suppliers” had the first priorities among PA and PC, respectively. Research limitations/implications While the proposed approach has many advantages, filling the matrixes is time-consuming. Since illustrating the 3D matrix was not possible, the matrix was separated into five two-dimensional matrixes. Originality/value Compared to the studied literature, the proposed approach is practically new in the post bank services.

Matrix form of interval multivariable gray model and its application

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Sandang Guo ◽  
Yaqian Jing ◽  
Bingjun Li
Keyword(s):  
Three Dimensional ◽  
Original Data ◽  
Upper Bounds ◽  
Matrix Form ◽  
Gray Model ◽  
Interval Numbers ◽  
Content Type ◽  
The Matrix ◽  
Number Sequences ◽  
The Difference

PurposeThe purpose of this paper is to make multivariable gray model to be available for the application on interval gray number sequences directly, the matrix form of interval multivariable gray model (IMGM(1,m,k) model) is constructed to simulate and forecast original interval gray number sequences in this paper.Design/methodology/approachFirstly, the interval gray number is regarded as a three-dimensional column vector, and the parameters of multivariable gray model are expressed in matrix form. Based on the dynamic gray action and optimized background value, the interval multivariable gray model is constructed. Finally, two examples and comparisons are carried out to verify the effectiveness of IMGM(1,m,k) model.FindingsThe model is applied to simulate and predict expert value, foreign direct investment, automobile sales and steel output, respectively. The results show that the proposed model has better simulation and prediction performance than another two models.Practical implicationsDue to the uncertainty information and continuous changing of reality, the interval gray numbers are used to characterize full information of original data. And the IMGM(1,m,k) model not only considers the characteristics of parameters changing with time but also takes into account information on lower, middle and upper bounds of interval gray numbers simultaneously to make better suitable for practical application.Originality/valueThe main contribution of this paper is to propose a new interval multivariable gray model, which considers the interaction between the lower, middle and upper bounds of interval numbers and need not to transform interval gray number sequences into real sequences. According to combining different characteristics of each bound of interval gray numbers, the matrix form of interval multivariable gray model is established to simulate and forecast interval gray numbers. In addition, the model introduces dynamic gray action to reflect the changes of parameters over time. Instead of white equation of classic MGM(1,m), the difference equation is directly used to solve the simulated and predicted values.

scholarly journals Three-Dimensional In Vitro Staphylococcus aureus Abscess Communities Display Antibiotic Tolerance and Protection from Neutrophil Clearance

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Marloes I. Hofstee ◽  
Martijn Riool ◽  
Igors Terjajevs ◽  
Keith Thompson ◽  
Martin J. Stoddart ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Cells ◽  
Early Stage ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Maximum Size ◽  
Human Neutrophils ◽  
Content Type

ABSTRACT Staphylococcus aureus is a prominent human pathogen in bone and soft-tissue infections. Pathophysiology involves abscess formation, which consists of central staphylococcal abscess communities (SACs), surrounded by a fibrin pseudocapsule and infiltrating immune cells. Protection against the ingress of immune cells such as neutrophils, or tolerance to antibiotics, remains largely unknown for SACs and is limited by the lack of availability of in vitro models. We describe a three-dimensional in vitro model of SACs grown in a human plasma-supplemented collagen gel. The in vitro SACs reached their maximum size by 24 h and elaborated a fibrin pseudocapsule, as confirmed by electron and immunofluorescence microscopy. The in vitro SACs tolerated 100× the MIC of gentamicin alone and in combination with rifampin, while planktonic controls and mechanically dispersed SACs were efficiently killed. To simulate a host response, SACs were exposed to differentiated PLB-985 neutrophil-like (dPLB) cells and to primary human neutrophils at an early stage of SAC formation or after maturation at 24 h. Both cell types were unable to clear mature in vitro SACs, but dPLB cells prevented SAC growth upon early exposure before pseudocapsule maturation. Neutrophil exposure after plasmin pretreatment of the SACs resulted in a significant decrease in the number of bacteria within the SACs. The in vitro SAC model mimics key in vivo features, offers a new tool to study host-pathogen interactions and drug efficacy assessment, and has revealed the functionality of the S. aureus pseudocapsule in protecting the bacteria from host phagocytic responses and antibiotics.

Effects of plasma nitriding interlayer on adhesion and tribological behaviors of AlTiSiN coating

2021 ◽  
Vol 73 (6) ◽  
pp. 945-953
Author(s):  
Mengjuan Yin ◽  
Wenping Liang ◽  
Qiang Miao ◽  
Shiwei Zuo ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
Plasma Nitriding ◽  
Three Dimensional ◽  
Wear Property ◽  
The Novel ◽  
Content Type ◽  
The Matrix ◽  
Narrow Width ◽  
Glow Plasma ◽  
Excellent Adhesion ◽  
Ta15 Alloy

Purpose This study aims to the service life of TA15 alloy by solving the problem of the binding force between the matrix and AlTiSiN coating. The effect of a plasma nitriding (PN) interlayer on the magnetron-sputtered AlTiSiN coating was also investigated in detail. Design/methodology/approach The double-glow plasma alloying (DGPA) and magnetron sputtering (MS) techniques were combined as a new approach to realize a bilayer on TA15 consisting of an AlTiSiN layer with a PN interlayer. A TiN interlayer was formed via co-diffusion during the PN conducted at 1050°C for 3 h. Findings The PN interlayer can effectively improve the adhesion between coating and matrix; the PN/AlTiSiN coating presented excellent adhesion (80.1 N) and anti-wear property with a nano-hardness of 18.62 GPa. The resulting three-dimensional wear-track morphology exhibited a shallow depth and a narrow width. Originality/value The novel combination of the DGPA and MS technologies, using an infiltration layer rather than a coating one as the intermediate layer, can effectively enhance the adhesion between AlTiSiN coating and TA15 matrix. Meanwhile, the gradient layer can effectively improve both surface bearing and wear resistance.

Synergism between BCNU and irradiation in the treatment of anaplastic gliomas

1979 ◽  
Vol 51 (5) ◽  
pp. 581-586 ◽  
Author(s):  
Paul Steinbok ◽  
M. Stephen Mahaley ◽  
Raymond U ◽  
Douglas C. Zinn ◽  
Stan Lipper ◽  
...  
Keyword(s):  
Median Survival ◽  
Combined Therapy ◽  
Malignant Gliomas ◽  
Control Group ◽  
Therapeutic Effects ◽  
Survival Times ◽  
Content Type ◽  
Anaplastic Gliomas ◽  
In Series

✓ The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU was administered intraperitoneally as a single dose of 10 mg/kg. Two series of experiments were performed in order to duplicate the results. In Series 1, the median survival times of the experimental groups, in days after randomization, were as follows: control group (no treatment), 69; group receiving 2000 rads, 84 (p < 0.05); group receiving BCNU, 80.5 (p < 0.1); and group receiving 2000 rads + BCNU, 112 (p < 0.001). In Series 2, the median survival times were: control group, 73.5; group receiving 2300 rads, 85 (p < 0.01); group receiving BCNU, 92.5 (p < 0.025); and group receiving 2300 rads + BCNU, 123.5 (p < 0.001). In both series, combined therapy was significantly better than either radiation or BCNU alone. This is the first time that a synergistic effect of BCNU and irradiation has been reported in an in vivo brain-tumor model and supports the clinical use of this combination in the treatment of malignant gliomas.

Interstitial laser photochemotherapy of rhodamine-123-sensitized rat glioma

1987 ◽  
Vol 67 (6) ◽  
pp. 889-894 ◽  
Author(s):  
Stephen K. Powers ◽  
William C. Beckman ◽  
J. Tony Brown ◽  
Linda C. Kolpack
Keyword(s):  
Laser Light ◽  
Malignant Gliomas ◽  
Argon Laser ◽  
Rhodamine 123 ◽  
Adult Rats ◽  
Content Type ◽  
Rat Glioma ◽  
Original Tumor ◽  
Interstitial Laser

✓ The effect of interstitial laser photochemotherapy with the mitochondrial-specific intravital dye rhodamine-123 (Rh-123) was studied using a malignant rat glioma model system (RT2). Tumors were transplanted subcutaneously into the flank of athymic mice and into the cerebrum of adult rats. The Rh-123 photosensitization was produced by direct intratumoral injection of Rh-123 into the mouse RT2 flank tumors and by intravenous Rh-123 administration to adult rats with implanted RT2 intracerebral tumors. Intratumoral irradiation with 150 mW of argon laser light for an exposure time of 15 minutes was performed using a conical sapphire-tipped quartz optical fiber. Control groups of animals received either no treatment, Rh-123 injections, or administration of 150 mW of argon laser light for 15 minutes. Both flank and intracerebral tumors showed progressive diminution in size after treatment with Rh-123 photochemotherapy. There was no evidence of tumor recurrence in 60% of Rh-123 photochemotherapy-treated tumors. Recurrences in tumors treated with Rh-123 photochemotherapy usually appeared at the periphery of the original tumor at 10 days after treatment. Histologically, photochemotherapy-treated intracerebral tumors showed progressive shrinkage with increasing tumor necrosis over time. The finding of residual or recurrent tumor at the periphery of the original tumor mass suggests that the lack of penetration of the blue-green (argon) light was responsible for preventing complete tumor ablation. Our results suggest that Rh-123 photochemotherapy can destroy malignant gliomas in vivo; however, the poor penetrability of the photoactivating blue-green light may limit the effectiveness of this treatment for large or extensively invasive tumors.

scholarly journals Three-Dimensional Computer Model of Brainstem Respiratory Neuronal Circuits - Application for Research in Respirology

2013 ◽  
Vol 13 (Supplement-1) ◽  
pp. 7-14
Author(s):  
S. Gavliakova ◽  
J. Plevkova ◽  
J. Jakus ◽  
I. Poliacek
Keyword(s):  
Programming Languages ◽  
Computer Model ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Neuronal Circuits ◽  
Spatial Image ◽  
The Matrix ◽  
Computationally Intensive ◽  
High Level

Abstract Methods that had been applied to study central neuronal circuits regulating cough and respiratory reflexes so far rely on recording performed in vivo, ex vivo, micro injecting and lesion methods. Based on the available data it is clear that this network is complicated, multilevel, holarchical, undergoing reconfiguration under afferent inputs. For many students and researchers it is complicated to get a virtual spatial image of these cooperating neuronal populations. The project was aimed to create graphical three-dimensional computer model of the brainstem using environment MATLAB and the matrix algebra to visualize neuron localization within the brainstem. Relevant data for the model had been taken from recent and also former research papers published in particular areas. This model may help scientists to visualize groups of neurons, help them to find targets for microinjecting or lesion studies together with stereotaxic positioning. The model is upgradeable and highly flexible for future use, research and teaching applications in MATLAB environment. MATLAB is a high-level language and interactive environment that enables you to perform computationally intensive tasks faster than with traditional programming languages

scholarly journals Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa

Microbiology ◽  
2020 ◽  
Vol 166 (12) ◽  
pp. 1171-1180 ◽  
Author(s):  
Esther Sweeney ◽  
Akshay Sabnis ◽  
Andrew M. Edwards ◽  
Freya Harrison
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ex Vivo ◽  
Clinical Success ◽  
Biofilm Growth ◽  
Content Type ◽  
The Matrix ◽  
Model Versus ◽  
High Doses

In vivo biofilms cause recalcitrant infections with extensive and unpredictable antibiotic tolerance. Here, we demonstrate increased tolerance of colistin by Pseudomonas aeruginosa when grown in medium that mimics cystic fibrosis (CF) sputum versus standard medium in in vitro biofilm assays, and drastically increased tolerance when grown in an ex vivo CF model versus the in vitro assay. We used colistin conjugated to the fluorescent dye BODIPY to assess the penetration of the antibiotic into ex vivo biofilms and showed that poor penetration partly explains the high doses of drug necessary to kill bacteria in these biofilms. The ability of antibiotics to penetrate the biofilm matrix is key to their clinical success, but hard to measure. Our results demonstrate both the importance of reduced entry into the matrix in in vivo-like biofilm, and the tractability of using a fluorescent tag and benchtop fluorimeter to assess antibiotic entry into biofilms. This method could be a relatively quick, cheap and useful addition to diagnostic and drug development pipelines, allowing the assessment of drug entry into biofilms, in in vivo-like conditions, prior to more detailed tests of biofilm killing.

Expanded spectrum of viral therapy in the treatment of nervous system tumors

1992 ◽  
Vol 77 (4) ◽  
pp. 590-594 ◽  
Author(s):  
James M. Markert ◽  
Donald M. Coen ◽  
Amy Malick ◽  
Toshihiro Mineta ◽  
Robert L. Martuza
Keyword(s):  
Cell Culture ◽  
Nervous System ◽  
Malignant Gliomas ◽  
Treated Group ◽  
Early Passage ◽  
Content Type ◽  
Nervous System Tumors ◽  
Viral Therapy ◽  
Subrenal Capsule

✓ Despite aggressive therapy, many nervous system neoplasms, including malignant gliomas, medulloblastomas, malignant meningiomas, and neurofibrosarcomas, maintain high mortality rates. The authors recently utilized a thymidine kinase-negative herpes simplex-1 mutant virus, dlsptk, with reduced neurovirulence, for the effective treatment of malignant human gliomas in cell culture and in nude mouse in vivo models. The range of human nervous system tumors that might be responsive to viral therapy is now expanded. Three medulloblastoma, four malignant or atypical meningioma, and five neurofibrosarcoma cell lines or early-passage tumors were treated with the dlsptk virus in cell culture. A cell death rate of at least 99% was evident in every tumor tested for at least one multiplicity of infection within 14 days after treatment. Control tumor cell cultures remained viable. To test dlsptk therapy in vivo, the authors treated human medulloblastoma subcutaneous xenografts with two doses of dlsptk. Mean growth ratios were significantly inhibited in the treated group when compared to control tumors, and there was a significant number of tumor regressions in the treated animals. Similar results were seen with human malignant meningioma xenografts in a subrenal capsule study. These results encourage the further investigation of viral therapy in the treatment of a broad spectrum of nervous system tumors refractory to conventional treatment methods.

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