scholarly journals Berberine Photo-Activation Potentiates Cytotoxicity in Human Astrocytoma Cells through Apoptosis Induction

2021 ◽  
Vol 11 (10) ◽  
pp. 942
Author(s):  
Francesca Carriero ◽  
Carolina Martinelli ◽  
Fabio Gabriele ◽  
Giulia Barbieri ◽  
Lisa Zanoletti ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
High Rate ◽  
Surgical Removal ◽  
Therapeutic Approaches ◽  
Tumor Cell Death ◽  
Apoptosis Pathway ◽  
Astrocytoma Cells ◽  
Astrocytoma Cell ◽  
The Central Nervous System ◽  
Photosensitizing Agent

Photodynamic therapy (PDT) has recently attracted interest as an innovative and adjuvant treatment for different cancers including malignant gliomas. Among these, Glioblastoma (GBM) is the most prevalent neoplasm in the central nervous system. Despite conventional therapeutic approaches that include surgical removal, radiation, and chemotherapy, GBM is characterized by an extremely poor prognosis and a high rate of recurrence. PDT is a physical process that induces tumor cell death through the genesis and accumulation of reactive oxygen species (ROS) produced by light energy interaction with a photosensitizing agent. In this contribution, we explored the potentiality of the plant alkaloid berberine (BBR) as a photosensitizing and cytotoxic agent coupled with a PDT scheme using a blue light source in human established astrocytoma cell lines. Our data mainly indicated for the combined BBR-PDT scheme a potent activation of the apoptosis pathway, through a massive ROS production, a great extent of mitochondria depolarization, and the sub-sequent activation of caspases. Altogether, these results demonstrated that BBR is an efficient photosensitizer agent and that its association with PDT may be a potential anticancer strategy for high malignant gliomas.

scholarly journals Exploring Novel Molecular Targets for the Treatment of High-Grade Astrocytomas Using Peptide Therapeutics: An Overview

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 490 ◽  
Author(s):  
Giulia Guidotti ◽  
Liliana Brambilla ◽  
Daniela Rossi
Keyword(s):  
Malignant Gliomas ◽  
Genetic Alterations ◽  
Cellular Heterogeneity ◽  
High Grade ◽  
Therapeutic Approaches ◽  
Average Survival ◽  
The Central Nervous System ◽  
Specific Receptors ◽  
Models Of Disease ◽  
Pharmacologically Active

Diffuse astrocytomas are the most aggressive and lethal glial tumors of the central nervous system (CNS). Their high cellular heterogeneity and the presence of specific barriers, i.e., blood–brain barrier (BBB) and tumor barrier, make these cancers poorly responsive to all kinds of currently available therapies. Standard therapeutic approaches developed to prevent astrocytoma progression, such as chemotherapy and radiotherapy, do not improve the average survival of patients. However, the recent identification of key genetic alterations and molecular signatures specific for astrocytomas has allowed the advent of novel targeted therapies, potentially more efficient and characterized by fewer side effects. Among others, peptides have emerged as promising therapeutic agents, due to their numerous advantages when compared to standard chemotherapeutics. They can be employed as (i) pharmacologically active agents, which promote the reduction of tumor growth; or (ii) carriers, either to facilitate the translocation of drugs through brain, tumor, and cellular barriers, or to target tumor-specific receptors. Since several pathways are normally altered in malignant gliomas, better outcomes may result from combining multi-target strategies rather than targeting a single effector. In the last years, several preclinical studies with different types of peptides moved in this direction, providing promising results in murine models of disease and opening new perspectives for peptide applications in the treatment of high-grade brain tumors.

scholarly journals Current and Future Gene Therapy for Malignant Gliomas

2003 ◽  
Vol 2003 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Takao Kanzawa ◽  
Hideaki Ito ◽  
Yasuko Kondo ◽  
Seiji Kondo
Keyword(s):  
Gene Therapy ◽  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Malignant Gliomas ◽  
Therapeutic Approaches ◽  
Average Life ◽  
Average Life Expectancy ◽  
Experimental Animal Models ◽  
The Central Nervous System

Malignant gliomas are the most common neoplasm in the central nervous system. When treated with conventional treatments including surgery, irradiation, and chemotherapy, the average life expectancy of the most malignant type, glioblastoma multiforme is usually less than 1 year. Therefore, gene therapy is expected to be an effective and possibly curative treatment. Many gene therapeutic approaches have demonstrated efficacy in experimental animal models. However, the current clinical trials are disappointing. This review focuses on current therapeutic genes/vectors/delivery systems/targeting strategies in order to introduce updated trends and hopefully indicate prospective gene therapy for malignant gliomas.

Targeting Glioblastoma: The Current State of Different Therapeutic Approaches

2021 ◽  
Vol 19 ◽  
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Elif Burce Elbasan ◽  
Busra Karacam ◽  
Mustafa Namik Oztanir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Carrier ◽  
Resistance Mechanisms ◽  
Surgical Removal ◽  
Therapeutic Approaches ◽  
Average Life Span ◽  
Current State ◽  
The Central Nervous System ◽  
Molecular Therapies ◽  
Patient Prognosis

Background: Glioma is the primary cancer of the central nervous system in adults. Among gliomas, glioblastoma is the most deadly and aggressive form with an average life span of 1 to 2 years. Despite implementing the rigorous standard care involving maximal surgical removal followed by concomitant radiation and chemotherapy, the patient prognosis remains poor. Due to the infiltrative nature of glioblastoma, chemo- and radio-resistance behavior of these tumors and lack of potent chemotherapeutic drugs, treatment of glioblastoma is still a big challenge. Objective: The goal of the present review is to shed some light on the present state of novel strategies including molecular therapies, immunotherapies, nanotechnology and combination therapies for patients with glioblastoma. Methodology: Peer reviewed literature was extracted via Embase, Ovid, PubMed and Google Scholar till the year 2020. Conclusion: Insufficient effect of chemotherapies for glioblastoma is more likely because of different drug resistance mechanisms and intrinsically complex pathological characteristics. Therefore, more advancement in various therapeutic approaches such as antitumor immune response, targeting growth regulatory and drug resistance pathways, enhancing drug delivery and drug carrier systems are required in order to establish an effective treatment approach for patients with glioblastoma.

Surgical treatment of transmissible venereal tumor (sticker sarcoma)

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Bougherara Hithem ◽  
Boukhechem Saïd ◽  
Aguezlane Abdelaziz ◽  
Benelhadj Khouloud ◽  
Aissi Adel
Keyword(s):  
Surgical Treatment ◽  
Cancer Cells ◽  
Treatment Method ◽  
High Rate ◽  
Surgical Removal ◽  
Characteristic Appearance ◽  
Recurrent Tumors ◽  
External Genital Organs

Background: Sticker sarcoma, also called venereal sarcoma or venereal lymphosarcomatosis, is a tumor of the external genital organs in females and males. In male animals the penis and foreskin (prepuce) are affected, in the female, it happens in vagina (vagina) and labia (vulva). The diagnosis of sticker sarcoma is based on the chronic discharge, the typical locations and the characteristic appearance of the tumor. Methods: We have relied on the treatment method on the complete surgical removal of all cancer cells that we can access. Results: After surgery, we notice recurrent tumors about six months after surgical treatment, indicating the need for other treatments in addition to surgery. Conclusion: Although spontaneous regressions of sticker sarcoma are documented (with permanent immunity), chemotherapy is the treatment of choice today. Irradiation should also be effective. If the tumor is only removed surgically, there is a high rate of recurrence, and this is what happened with the case that we treated, as the tumor reappeared after less than six months.

Healthy Gut, Healthy Brain: The Gut Microbiome in Neurodegenerative Disorders

2020 ◽  
Vol 20 (13) ◽  
pp. 1142-1153 ◽  
Author(s):  
Sreyashi Chandra ◽  
Md. Tanjim Alam ◽  
Jhilik Dey ◽  
Baby C. Pulikkaparambil Sasidharan ◽  
Upasana Ray ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodegenerative Disorders ◽  
The Body ◽  
Therapeutic Approaches ◽  
Cns Disorders ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Present Understanding ◽  
Lateral Sclerosis

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington’s disease (HD). Objective: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. Methods: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. Results: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. Conclusion: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.

scholarly journals Comparison of Genetic Variants and Manifestations of OTUD6B-Related Disorder: The First Mexican Case

2020 ◽  
Vol 8 ◽  
pp. 232470962095777 ◽  
Author(s):  
Maria Elena Romero-Ibarguengoitia ◽  
Consuelo Cantú-Reyna ◽  
Dalia Gutierrez-González ◽  
Héctor Cruz-Camino ◽  
Arnulfo González-Cantú ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Genetic Variants ◽  
Therapeutic Approaches ◽  
Multisystem Disorder ◽  
Related Disorder ◽  
Dysmorphic Features ◽  
The Third ◽  
The Central Nervous System ◽  
Mexican Patient

The intellectual disability syndrome characterized by seizures and dysmorphic features was initially described in 2017 and was associated with genetic variants in the OTUD6B gene, identified by exome sequencing (ES) in a large cohort. This multisystem disorder primarily affects the central nervous system, the gastrointestinal, and the skeletal systems. In this article, we describe the first Mexican patient diagnosed by ES. The homozygous c.433C>T (p.Arg145*) variant of the OTUD6B gene confirmed this intellectual disability syndrome. In addition to seizures and other more frequently reported manifestations of this condition, this is the third patient with associated hypothyroidism and hypogammaglobulinemia, underscoring the value of screening for these conditions in other patients. The current challenge with this patient is to ensure medical management of his seizures and provide him with a better quality of life. The possibilities of additional therapeutic approaches may increase by understanding the physiopathology of the involved pathways.

Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1

2004 ◽  
Vol 287 (5) ◽  
pp. C1282-C1291 ◽  
Author(s):  
James K. Bubien ◽  
Hong-Long Ji ◽  
G. Yancey Gillespie ◽  
Catherine M. Fuller ◽  
James M. Markert ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Outward Current ◽  
Whole Cell ◽  
Amino Acid Peptide ◽  
Cation Selectivity ◽  
Astrocytoma Cells ◽  
Acid Sensing Ion Channels ◽  
Inward Currents ◽  
Cell Current ◽  
Peptide Toxin

Psalmotoxin 1 (a component of the venom of a West Indies tarantula) is a 40-amino acid peptide that inhibits cation currents mediated by acid-sensing ion channels (ASIC). In this study we performed electrophysiological experiments to test the hypothesis that Psalmotoxin 1 (PcTX1) inhibits Na+ currents in high-grade human astrocytoma cells (glioblastoma multiforme, or GBM). In whole cell patch-clamped cultured GBM cells, the peptide toxin quickly and reversibly inhibited both inward and outward current with an IC50 of 36 ± 2 pM. The same inhibition was observed in freshly resected GBM cells. However, when the same experiment was performed on normal human astrocytes, the toxin failed to inhibit the whole cell current. We also determined a cationic selectivity sequence for inward currents in three cultured GBM cell lines (SK-MG-1, U87-MG, and U251-MG). The selectivity sequence yielded a unique biophysical fingerprint with inward K+ conductance approximately fourfold greater than that of Na+, Li+, and Ca2+. These observations suggest that PcTX1 may prove useful in determining whether GBM cells express a specific ASIC-containing ion channel type that can serve as a target for both diagnostic and therapeutic treatments of aggressive malignant gliomas.

DDRE-50. INVESTIGATING THE ROLE OF LonP1 IN GLIOBLASTOMA TUMOR PROGRESSION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi85-vi85
Author(s):  
Christopher Douglas ◽  
Daniela Bota ◽  
Kaijun Di ◽  
Bhaskar Das ◽  
Javier Lepe
Keyword(s):  
Tumor Progression ◽  
Malignant Gliomas ◽  
Xenograft Model ◽  
Treatment Resistance ◽  
Proteasome Inhibition ◽  
High Rate ◽  
Who Grade ◽  
Dismal Prognosis ◽  
Stem Cell Lines ◽  
Novel Strategy

Abstract Glioblastoma (GBM), a WHO grade IV brain cancer, exhibits strong treatment resistance and a high rate of reoccurrence, which gives it a dismal prognosis, a 5% survival rate in the first 5 years. LonP1, a mitochondrial master regulator, can drive metabolic transformation, cytokine production, EMT, and treatment resistance in various cancer types, but its role in GBM remains unexplored. Our research group has previously shown that LonP1 is overexpressed in human malignant gliomas, particularly glioblastoma, and that this is associated with disease prognosis. Here, we present findings that demonstrate that LonP1 seems to drive enhanced tumor progression, invasiveness, angiogenesis in different high grade glioblastomas based on TCGA-subtype. Furthermore, in collaboration with Professor Bhaskar Das, we have validated a lead compound, BT317, with on-target inhibition of LonP1 protease activity. BT317 has enhanced activity against glioma stem cell lines (GSC) and has demonstrated low toxicity and efficacy in an intracranial xenograft model. This preliminary data highlights the potential of using combinatorial, pharmacological LonP1 and proteasome inhibition as a novel strategy for targeting specific subtypes of GBM.

Veterinary approaches to canine mammary tumors and knowledge of the consensus statement in Brazil

2021 ◽  
Vol 14 (1) ◽  
pp. 24-28
Author(s):  
Tainá Zuchi ◽  
◽  
Claudia Lopatini ◽  
Joice Faria
Keyword(s):  
Consensus Statement ◽  
Immunohistochemical Analysis ◽  
Mammary Tumors ◽  
Surgical Removal ◽  
Therapeutic Approaches ◽  
Canine Mammary Tumors ◽  
Preventive Actions ◽  
Criteria For Diagnosis ◽  
Unilateral Mastectomy

Mammary gland tumors are one of the most commonly diagnosed tumors in female dogs, with a reported prevalence ranging from 26 to 73% in Brazil. In recognition of the importance of these tumors veterinary researchers and clinicians in Brazil produced the first consensus statement regarding canine mammary tumors in 2010. The intention was to establish criteria for diagnosis, prognosis, and treatment. This study evaluated the methods of prevention, diagnosis, treatment, and determination of prognosis used by veterinarians in Brazil, and sought to quantify the number of veterinarians who were aware of the consensus statement. One hundred and three veterinary clinics participated in the study, 87.37% of which recommend early neutering as a preventative treatment for mammary tumors. For diagnosis, 100% of these use laboratory testing, 94.17% perform chest radiography, 78.64% incisional biopsies, 44.66% cytological analysis, and 13.59% immunohistochemical analysis. The most common surgical procedure is unilateral mastectomy (72.81%), and chemotherapy is performed in 49.51% of the clinics. Of the 103 clinics, 66.01% were aware of the consensus. Although knowledge of the consensus statement is widespread among veterinarians in Brazil, not all its recommendations are being followed. Preventive actions for canine mammary tumors are well established in most parts of the country. However, the consensus statement has had little influence on informing prognostic and therapeutic approaches, with a poor uptake of surgical removal of lymph nodes and immunohistochemical examination.

Evaluation of the Autonomic Nervous System Changes and Temporal-Spatial Gait Analysis in Patients with Ischemic Stroke Subjected to Neurorehabilitation Conventional Methods and Using Special. Literature Revie

2021 ◽  
Vol 63 (1) ◽  
pp. 65-70
Author(s):  
Sebastian Szyper ◽  
Paweł Zalewski
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Brain Plasticity ◽  
High Rate ◽  
Global Literature ◽  
Autonomic Nervous ◽  
Gait Quality ◽  
Therapeutic Concepts ◽  
The Central Nervous System ◽  
Quality Material

Introduction: The persistent high rate of disability in people after stroke in Poland and globally requires continuous analysis of the effectiveness of rehabilitation. This review of the global literature analyzes the effectiveness of two therapeutic concepts in relation to changes in the autonomic nervous system and gait quality. Material and Methods: We searched PubMed for available literature using keywords. The search included literature available in English between January 2000 and June 2017. Results: Most studies described in this literature review did not show any significant advantage in terms of effectiveness of neurorehabilitation methods over conventional ones. Conclusions: The effectiveness of rehabilitation focuses mainly on modulating brain plasticity associated with neurologic deficits in the central nervous system, ignoring the autonomic nervous system.

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