Modification of Early Radiation Death in Guinea Pigs

1956 ◽  
Vol 187 (2) ◽  
pp. 378-380 ◽  
Author(s):  
H. L. Andrews ◽  
K. C. Brace
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Time ◽  
Radiation Protection ◽  
Guinea Pigs ◽  
Muscular Activity ◽  
Anticonvulsant Drugs ◽  
Whole Body ◽  
Convulsive Activity ◽  
Early Radiation

A series of depressant and anticonvulsant drugs has been used in an attempt to modify the ‘early’ or ‘central nervous system’ death in guinea pigs. Pentobarbital given in anesthetic doses prior to irradiation dramatically alters the course of injury induced by whole body doses of 6000 r or more. Survival time is sharply increased and all signs of convulsions and hyperexcitability are suppressed. Phenobarbital and paraldehyde show similar actions, but the margin of safe dosage is smaller than with pentobarbital. The action of pentobarbital appears to be a true radiation protection. Other drugs, such as diphenyl hydantoinate suppress convulsive activity and lengthen survival time slightly. This is probably due to a sparing action from the intense muscular activity associated with the convulsions. None of the drugs tested showed an effect when given after irradiation.

EXTH-14. PRECLINICAL EVALUATION OF NOVEL CDK4/6 INHIBITOR GLR2007 IN GLIOBLASTOMA MODELS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi166-vi166
Author(s):  
Lei Yin ◽  
Zhenglin Yao ◽  
Yue Wang ◽  
Ying-Hui Huang ◽  
Michelle Mazuranic ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Time ◽  
Whole Body ◽  
Vehicle Group ◽  
Tumor Growth Inhibition ◽  
Preclinical Studies ◽  
In Vivo Evaluation ◽  
Xenograft Models ◽  
Change In Mean

Abstract Glioblastoma multiforme (GBM) is characterized by a high frequency of cyclin-dependent kinase (CDK)4 and CDK6 pathway dysregulation. None of the approved CDK4/6 inhibitors are indicated for GBM. Poor blood–brain barrier (BBB) penetration is a potential factor limiting treatment efficacy in GBM. GLR2007 is an investigational CDK4/6 inhibitor with the potential for improved penetration across the BBB. These preclinical studies investigated the anti-tumor efficacy in GBM xenograft models and central nervous system distribution of GLR2007. In vivo evaluation of the anti-tumor efficacy of GLR2007 versus vehicle, abemaciclib, and/or palbociclib was performed in two BALB/c nude mouse GBM xenograft models. Efficacy was expressed as tumor growth inhibition (TGI, change in mean tumor volume from baseline as a percentage of change in vehicle group) or increased survival time. Following 21 days of treatment, TGI in BN2289 subcutaneous xenografts was 39.4% and 56.4% for 25 mg/kg and 50 mg/kg GLR2007 groups, respectively, 34.0% for 25 mg/kg palbociclib, and 24.9% for 25 mg/kg abemaciclib (p < 0.001 in all groups vs vehicle control). In U87-luc orthotopic xenografts, compared with vehicle controls, median survival time was 50.0% (p = 0.0009) longer in the 12.5 mg/kg GLR2007 group, similar to the 150 mg/kg abemaciclib group (54.4%, p = 0.0002), and was 182.6% (p < 0.0001) longer in mice treated with 50 mg/kg GLR2007. Quantitative whole-body autoradiography was used to determine the distribution of [14C]GLR2007 in Sprague Dawley rats following a single oral dose. Total radioactivity levels in the brain exceeded those in plasma by 2.3–4.5-fold from 2–6 h after dosing. These preclinical studies suggest the potential of GLR2007 for the treatment of GBM, supported by evidence that GLR2007 showed numerically greater anti-tumor efficacy than approved CDK4/6 inhibitors palbociclib and abemaciclib in GBM xenograft models, and evidence of substantial central nervous system distribution.

Synthesis and Evaluation of 18F-INER-1577-3 as a Central Nervous System (CNS) Histone Deacetylase Imaging Agent

2020 ◽  
Vol 16 (8) ◽  
pp. 978-990
Author(s):  
Ming-Hsin Li ◽  
Han-Chih Chang ◽  
Chun-Fang Feng ◽  
Hung-Wen Yu ◽  
Chyng-Yann Shiue
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Histone Deacetylases ◽  
Authentic Sample ◽  
Cancer Cell Line ◽  
Radiochemical Yield ◽  
Imaging Agent ◽  
Whole Body ◽  
Imaging Agents ◽  
Synthesis Time

Background:: Epigenetic dysfunction is implicated in many neurologic, psychiatric and oncologic diseases. Consequently, histone deacetylases (HDACs) inhibitors have been developed as therapeutic and imaging agents for these diseases. However, only a few radiotracers have been developed as HDACs imaging agents for the central nervous system (CNS). We report herein the synthesis and evaluation of [18F]INER-1577-3 ([18F]5) as an HDACs imaging agent for CNS. Methods:: [18F]INER-1577-3 ([18F]5) was synthesized by two methods: one-step (A) and two-step (B) methods. Briefly, radiofluorination of the corresponding precursors (11, 12) with K[18F]/K2.2.2 followed by purifications with HPLC gave ([18F]5). The quality of [18F]INER- 1577-3 synthesized by these methods was verified by HPLC and TLC as compared to an authentic sample. The inhibitions of [18F]INER-1577-3 and related HDACs inhibitors on tumor cells growth were carried out with breast cancer cell line 4T1 and MCF-7. The whole-body and brain uptake of [18F]INER-1577-3 in rats and AD mice were determined using a micro-PET scanner and the data was analyzed using PMOD. Results: : The radiochemical yield of [18F]INER-1577-3 synthesized by these two methods was 1.4 % (Method A) and 8.8% (Method B) (EOB), respectively. The synthesis time was 115 min and 100 min, respectively, from EOB. The inhibition studies showed that INER-1577-3 has a significant inhibitory effect in HDAC6 and HDAC8 but not HDAC2. PET studies in rats and AD mice showed a maximum at about 15 min postinjection for the whole brain of a rat (0.47 ± 0.03 %ID/g), SAMP8 mice (5.63 ± 1.09 %ID/g) and SAMR1 mice (7.23 ± 1.21 %ID/g). Conclusion:: This study showed that INER-1577-3 can inhibit tumor cell growth and is one of a few HDACs inhibitors that can penetrate the blood-brain barrier (BBB) and monitor HDAC activities in AD mice. Thus, [18F]INER-1577-3 may be a potent HDACs imaging agent, especially for CNS.

scholarly journals ML-23 The outcome of malignant lymphoma of the central nervous system in a single institution

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii18-ii18
Author(s):  
Kiyonori Kuwahara ◽  
Shigeo Ohba ◽  
Kazuyasu Matsumura ◽  
Saeko Higashiguchi ◽  
Daijiro Kojima ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adverse Events ◽  
Malignant Lymphoma ◽  
Survival Time ◽  
Progression Free Survival ◽  
Treatment Method ◽  
The Other ◽  
High Dose ◽  
Other Hand

Abstract Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.

Bone-brain crosstalk and potential associated diseases

2016 ◽  
Vol 28 (2) ◽  
Author(s):  
Audrey Rousseaud ◽  
Stephanie Moriceau ◽  
Mariana Ramos-Brossier ◽  
Franck Oury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cognitive Functions ◽  
Intimate Relationship ◽  
Whole Body ◽  
Reciprocal Relationships ◽  
Skeletal Homeostasis ◽  
The Central Nervous System ◽  
The Brain

AbstractReciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.

scholarly journals An overlooked cause of longitudinally extensive spinal cord lesions: Primary central nervous system lymphoma

2020 ◽  
Author(s):  
Meng Wang ◽  
Baochang Qi ◽  
Jinming Han ◽  
Chunjie Guo ◽  
Limei Qu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Lower Limbs ◽  
Whole Body ◽  
Sensory Loss ◽  
High Dose ◽  
Spinal Cord Lesions

Abstract Background: Primary central nervous system lymphoma (PCNSL ) is a rare and aggressive malignant tumor. It is easy to be misdiagnosed due to its low incidence and unspecific presentations in clinical practice. PCNSL mainly occurs intracranially in the brain while spinal cord is rarely involved. Case presentation: Here we report a 76-year-old woman who had a suspicious tumor history and presented retardant paralysis, bladder dysfunction and sensory loss of the lower limbs. Magnetic resonance imaging (MRI) of the thoracic spine disclosed longitudinally extensive lesions extending from thoracic 4 (T4) to lumbar 1 (L1) vertebral level with an enhanced nodular lesion noting at levels of T10 and T11 . In order to further identify the cause, the whole body 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) was performed and showed a hypermetabolic nodule corresponded to MRI enhancing lesions, which further suggesting the possibility of a tumor. The patient then underwent a surgical resection and spinal cord biopsy confirmed the diagnosis of non-Hodgkin's lymphoma (diffuse large B-cell type). The patient then received a high-dose chemotherapy based on methotrexate combined with Rituximab. Unfortunately, the symptoms of this patient have not been improved significantly after three rounds of chemotherapy. Conclusion: Our case indicates that PCNSL may also serve as a possible cause for longitudinally extensive spinal cord lesions, especially the patients who had a suspicious tumor history, MRI enhancing lesion s in the spinal cord corresponded to hypermetabolic nodules on 18 F-FDG- PET/CT at the same level.

Biotransport to the Cerebral Tissues Related to the Vascular Diseases

2008 ◽  
Author(s):  
Kazuo Tanishita ◽  
Kazuto Masamoto ◽  
Iwao Kanno ◽  
Hirosuke Kobayashi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Oxygen Transport ◽  
Consumption Rate ◽  
Vascular Diseases ◽  
Selective Vulnerability ◽  
Whole Body ◽  
Sensorimotor Function ◽  
Irreversible Damage

Brain is a highly oxidative organ and its consumption rate of oxygen accounts for 20 percent of that of the whole body. This large consumption rate must be met by continuous supply of oxygen, because lack of oxygen rapidly causes irreversible damage to central nervous system. Acute hypoxic episodes cause a certain pattern of regional damage. Cerebral cortex (e.g., layers III, V, and VI) is one of the most susceptible regions to hypoxia, and damage to sensorimotor function is particularly severe in humans that survive hypoxic/ischemic episodes. However, little is known about whether oxygen transport in intracortical regions relates to such selective vulnerability to hypoxia.

scholarly journals A PARALYTIC DISEASE OF GUINEA PIGS DUE TO THE TUBERCLE BACILLUS

1929 ◽  
Vol 50 (3) ◽  
pp. 365-370 ◽  
Author(s):  
Richard E. Shope ◽  
Paul A. Lewis
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tuberculous Meningitis ◽  
Guinea Pigs ◽  
Tuberculous Infection ◽  
Tubercle Bacillus ◽  
Herpes Encephalitis ◽  
Subsequent Publication ◽  
The Central Nervous System ◽  
Rule Out

The experimental data collected during this study of a transmissible type of paralysis developing in tuberculous guinea pigs indicate the condition to be a true tuberculous meningitis. We have been able to rule out the possibility that it is due to a non-tuberculous infection of the central nervous system caused by Roemer's virus, or by an atypical herpes virus, or by some bacterium other than the tubercle bacillus. Roemer's virus and herpes could be eliminated from consideration when Berkefeld N filtrates of infectious brain emulsions proved incapable of reproducing the disease. Furthermore, rabbits could be infected as they cannot with Roemer's virus, and the disease elicited in rabbits bears no semblance to herpes encephalitis. No organism other than the tubercle bacillus could be obtained on culturing brain or brain emulsions from experimental cases, and no others were seen in examining fresh smear preparations from the central nervous system. In a modified Noguchi medium a tubercle bacillus possessing atypical staining properties was obtained. This organism was capable of producing the typical paralytic disease when injected intracerebrally into guinea pigs, and also generalized tuberculosis in animals inoculated subcutaneously with it. Typical tuberde bacilli were readily demonstrable in sections of the meninges from animals with the disease, and culture of pieces of brain on Dorset's egg medium usually yielded a growth of tubercle bacilli. Only in the first of the experimental passages, on the other hand, was it possible to demonstrate acid-fast organisms in fresh smear preparations from the central nervous system. This fact and the attributes of the atypically staining organisms encountered in the cultures in Noguchi media will be considered more fully in a subsequent publication. In view of the much discussed question of the filtrability of the tubercle bacillus our observations concerning the failure of this organism to pass a Berkefeld N filter are of interest. No animal in our series inoculated intracerebrally with brain emulsion from either a "spontaneous" or experimental case of tuberculous meningitis failed to develop meningitis, and that rather acutely, while no animal in our series injected with a Berkefeld filtrate of brain emulsion has developed tuberculous meningitis or any other form of tuberculosis. In connection with this observation it must be recalled that the organism was atypical in respect to its staining qualities at least.

Angiopep-2 conjugated nanoparticles loaded with doxorubicin for the treatment of primary central nervous system lymphoma

2020 ◽  
Vol 8 (5) ◽  
pp. 1290-1297 ◽  
Author(s):  
Xiao-Xiao Shi ◽  
Wei-Min Miao ◽  
Di-Wen Pang ◽  
Jia-Si Wu ◽  
Qi-Song Tong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Time ◽  
Central Nervous System Lymphoma

APP nanoparticle was developed to deliver DOX for the treatment of PCNSL. The results indicated that APP@DOX could overcome the BBB, and significantly prolong the survival time of mice with an intracranial SU-DHL-2 lymphoma xenograft.

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