scholarly journals Pathogenetic Features and Current Management of Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 856
Author(s):  
Hong-My Nguyen ◽  
Kirsten Guz-Montgomery ◽  
Devin B. Lowe ◽  
Dipongkor Saha
Keyword(s):  
Poor Prognosis ◽  
Treatment Options ◽  
Clinical Status ◽  
Treatment Resistance ◽  
Micro Rna ◽  
Current Management ◽  
Small Molecule Drugs ◽  
Adults And Children ◽  
Rigorous Treatment ◽  
Primary Malignant Brain Tumor

Glioblastoma (GBM) is the most common form of primary malignant brain tumor with a devastatingly poor prognosis. The disease does not discriminate, affecting adults and children of both sexes, and has an average overall survival of 12–15 months, despite advances in diagnosis and rigorous treatment with chemotherapy, radiation therapy, and surgical resection. In addition, most survivors will eventually experience tumor recurrence that only imparts survival of a few months. GBM is highly heterogenous, invasive, vascularized, and almost always inaccessible for treatment. Based on all these outstanding obstacles, there have been tremendous efforts to develop alternative treatment options that allow for more efficient targeting of the tumor including small molecule drugs and immunotherapies. A number of other strategies in development include therapies based on nanoparticles, light, extracellular vesicles, and micro-RNA, and vessel co-option. Advances in these potential approaches shed a promising outlook on the future of GBM treatment. In this review, we briefly discuss the current understanding of adult GBM’s pathogenetic features that promote treatment resistance. We also outline novel and promising targeted agents currently under development for GBM patients during the last few years with their current clinical status.

scholarly journals Glioblastoma and MiRNAs

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1581
Author(s):  
Swalih P. Ahmed ◽  
Javier S. Castresana ◽  
Mehdi H. Shahi
Keyword(s):  
Brain Tumors ◽  
Human Body ◽  
Diagnostic Tool ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Diagnosis And Treatment ◽  
Therapeutic Success ◽  
Knowing That ◽  
Almost All ◽  
Cell Signaling Pathways

Glioblastoma (GB) is one of the most common types of lethal brain tumors. Although several treatment options are available including surgery, along with adjuvant chemo and radiotherapy, the disease has a poor prognosis and patients generally die within 14 months of diagnosis. GB is chemo and radio resistant. Thus, there is a critical need for new insights into GB treatment to increase the chance of therapeutic success. This is why microRNA (miRNA) is being potentially considered in the diagnosis and treatment of glioblastoma. The objective of our review is to provide a holistic picture of GB up-regulated and down-regulated miRNA, in relationship with the expression of other genes, cell signaling pathways, and their role in GB diagnosis and treatment. MiRNA treatment is being considered to be used against GB together with radiotherapy and chemotherapy. Moreover, the use of miRNA as a diagnostic tool has also begun. Knowing that miRNAs are isolated in almost all human body fluids and that there are more than 3000 miRNAs in the human genome, plus the fact that each miRNA controls hundreds of different mRNAs, there is still much study needed to explore how miRNAs relate to GB for its proliferation, progression, and inhibition.

scholarly journals Advances in Targeting Cutaneous Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2090
Author(s):  
Dimitri Kasakovski ◽  
Marina Skrygan ◽  
Thilo Gambichler ◽  
Laura Susok
Keyword(s):  
Cutaneous Melanoma ◽  
Clinical Investigation ◽  
Early Stage ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Immune Checkpoint Blockade ◽  
Oncolytic Viruses ◽  
Cancer Site ◽  
Western World ◽  
Pharmacological Agents

To date, the skin remains the most common cancer site among Caucasians in the western world. The complex, layered structure of human skin harbors a heterogenous population of specialized cells. Each cell type residing in the skin potentially gives rise to a variety of cancers, including non-melanoma skin cancer, sarcoma, and cutaneous melanoma. Cutaneous melanoma is known to exacerbate and metastasize if not detected at an early stage, with mutant melanomas tending to acquire treatment resistance over time. The intricacy of melanoma thus necessitates diverse and patient-centered targeted treatment options. In addition to classical treatment through surgical intervention and radio- or chemotherapy, several systemic and intratumoral immunomodulators, pharmacological agents (e.g., targeted therapies), and oncolytic viruses are trialed or have been recently approved. Moreover, utilizing combinations of immune checkpoint blockade with targeted, oncolytic, or anti-angiogenic approaches for patients with advanced disease progression are promising approaches currently under pre-clinical and clinical investigation. In this review, we summarize the current ‘state-of-the-art’ as well as discuss emerging agents and regimens in cutaneous melanoma treatment.

scholarly journals Lomeguatrib Increases the Radiosensitivity of MGMT Unmethylated Human Glioblastoma Multiforme Cell Lines

2021 ◽  
Vol 22 (13) ◽  
pp. 6781
Author(s):  
Anna Kirstein ◽  
Daniela Schilling ◽  
Stephanie E. Combs ◽  
Thomas E. Schmid
Keyword(s):  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Dna Methyltransferase ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Cell Cycle Distribution ◽  
Human Glioblastoma ◽  
Human Glioblastoma Multiforme ◽  
Mgmt Protein

Background: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. In particular, the O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. Methods: Lomeguatrib, a highly specific MGMT inhibitor, was used to inactivate MGMT protein in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. Results: Lomeguatrib significantly decreased MGMT protein and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. Conclusion: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect.

scholarly journals Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 532
Author(s):  
Dorota Wesół-Kucharska ◽  
Dariusz Rokicki ◽  
Aleksandra Jezela-Stanek
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Clinical Picture ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Mitochondrial Diseases ◽  
Energy Deficit ◽  
Atp Production ◽  
Current State

Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children. The onset of epilepsy is associated with poor prognosis, while its treatment is very challenging, which further adversely affects the course of these disorders. Fortunately, our knowledge of mitochondrial diseases is still growing, which gives hope for patients to improve their condition in the future. The paper presents the pathophysiology, clinical picture and treatment options for epilepsy in patients with mitochondrial disease.

scholarly journals Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Costas Tsioufis ◽  
Athanasios Kordalis ◽  
Dimitris Flessas ◽  
Ioannis Anastasopoulos ◽  
Dimitris Tsiachris ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Resistant Hypertension ◽  
Antihypertensive Treatment ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Obstructive Sleep ◽  
Cardiovascular Morbidity And Mortality ◽  
Sympathetic Nervous

Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

scholarly journals Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment ?

2019 ◽  
Author(s):  
Seul-Ki Choi ◽  
Heejin Kam ◽  
Kye-Young Kim ◽  
Suk In Park ◽  
Yun-Sil Lee
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Treatment ◽  
Poor Prognosis ◽  
Treatment Resistance ◽  
Therapeutic Agents ◽  
Heat Shock Protein 27 ◽  
Cytoskeletal Remodeling ◽  
Protein Chaperone

Heat shock protein 27 (HSP27), induced by heat shock, environmental, and pathophysiological stressors, is a multi-dimensional protein that acts as a protein chaperone and an antioxidant. HSP27 plays a major role in the inhibition of apoptosis and actin cytoskeletal remodeling. HSP27 is upregulated in many cancers and is associated with poor prognosis, as well as treatment resistance whereby cells are protected from therapeutic agents that normally induce apoptosis. This review highlights the most recent findings and role of HSP27 in cancer, as well as strategies for using HSP27 inhibitors for therapeutic purposes.

Abstract 3490: Perfusion Defect Is Associated With Poor Prognosis Of Lacunar Infarction.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Jeong Jin Park ◽  
Na-Young Ryoo ◽  
Joung-Ho Rha ◽  
Hee-Kwon Park
Keyword(s):  
Regression Analysis ◽  
Propensity Score ◽  
Perfusion Defect ◽  
Poor Prognosis ◽  
Small Vessel Disease ◽  
Clinical Status ◽  
Current Smoker ◽  
Parent Artery ◽  
Poor Outcomes

Backgrounds: Small subcortical infarctions are caused by lipohyalinosis and also by microatheroma and microembolism. However, it remained still unknown which clinical or radiological findings could be useful for prediction of long-term prognosis. We sought to find whether perfusion images are associated with long-term poor clinical status. Methods: We reviewed 197 patients who admitted from January, 2009 to January, 2011, and who had the lacunae(≤20mm) in the perforator territory of the middle cerebral artery on diffusion-weight MRI(DWI) within 3 days of onset. T2 weighted imaging and perfusion-weighted MRI(PWI) were evaluated in all participants. We divided the patients according to the existence of perfusion defect and analyzed the association between perfusion defect and poor outcomes, defined as modified Rankin score(mRS)≥3 at 3 months Results: Among a total 197 patients(69 Men; 63.8±11.2y), 78 subjects(52 Men; 62.4±12.1y) had the perfusion defect on PWI. The subject with perfusion defect had the higher frequency of current smoker(P=0.03) and poor outcomes at 3 months (P=0.002), compared to those without. There was no difference in other risk factors, infarct size or parent artery stenosis between two groups. Multivariate binary regression analysis showed that the perfusion defect was strongly associated with poor outcomes at 3 months(P=0.002;adjusted OR 4.21; adjusted 95% CI,1.73-10.28). The propensity score regression analysis also indicated that perfusion defect could predict the poor prognosis(Propensity score adjusted OR,3.88). Conclusion: Perfusion defect of small vessel disease seems to have the influence on the recovery after lacunae. Further study may be needed to find whether the PWI can be useful for diagnosing the various etiology of lacunae.

Neuroendovascular Management of Acute Ischemic Basilar Strokes: 2-Dimensional Operative Video

2021 ◽  
Author(s):  
Guilherme B F Porto ◽  
Mithun G Sattur ◽  
Sami Al Kasab ◽  
Alejandro M Spiotta ◽  
Adam Arthur ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Balloon Angioplasty ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Lessons Learned ◽  
Critical Flow ◽  
High Morbidity ◽  
Intracranial Atherosclerotic Disease ◽  
Catheter Size ◽  
Underlying Pathology

Abstract Basilar artery occlusions (BAOs) are devastating ischemic strokes that account for 1% of all strokes with high morbidity and mortality; however, neuroendovascular techniques such as ADAPT have recently revolutionized the clinical outcomes of these patients.1-3 Common underlying pathology in patients with BAO include intracranial atherosclerotic disease (ICAD) as well as thromboembolic origin.4 Basilar artery ICAD in a setting of acute stroke portends a poor prognosis and post-thrombectomy residual critical flow limiting stenosis treatment options, including balloon angioplasty with or without stent placement.5-7 We present a video illustration of neuroendovascular technique and challenges encountered when managing this pathology. Image at 5:42 reprinted with permission from Alawieh et al, Lessons learned over more than 500 stroke thrombectomies using ADAPT with increasing aspiration catheter size, Neurosurgery, 86(1), 2020, pp. 61-70, with permission from the Congress of Neurological Surgeons.1

Pediatric blinatumomab preparation: Risk assessment on SmPC for software compliance

2020 ◽  
pp. 107815522096639
Author(s):  
Mario Cirino ◽  
Riccardo Provasi ◽  
Irina Cebulec ◽  
Clara Palmieri ◽  
Paolo Schincariol ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Poor Prognosis ◽  
Computer Processing ◽  
Second Phase ◽  
Preparation Process ◽  
Critical Issues ◽  
Adults And Children ◽  
Two Phases ◽  
Set Up ◽  
Cancer In Children

Introduction Blinatumomab is an anticancer drug used in the treatment of Acute Lymphoblastic Leukaemia (ALL) in both adults and children. ALL is the most common form of cancer in children and patients who are refractory to standard treatments have poor prognosis. The preparation of blinatumomab is unique and extremely complex. It’s important to carry out any information to identify all the critical issues related to the preparation of blinatumomab: sharing procedure between prescribers, staff of the Centralized Chemotherapy Preparation Unit [Unità Farmaci Antiblastici (UFA)] and administering nurses aimed at reducing the clinical risk related to the management of the drug blinatumomab and to obtain correct prescriptions on the real dose to be prepared, safe worksheets with computer processing of all variables (volumes to be added and corresponding dose of drug) and complete labels containing all the information necessary for the control of the preparation and its correct infusion. Methods A computerized process involves the use of specific software to which precise instructions must be given. This study is divided into two phases, the first one focused on the analysis of Summary of Product Characteristics (SmPC) and the extrapolation of any unclear part of SmPC. The second phase involved the manufacturer to answer a questionnaire. Results This comparison with the company allowed to perfect the blinatumomab preparation process leading to: 1. allow the patient to be discharged and return a few times for infusions and consequently reduce the number of medical prescriptions; 2. set up the drug for each patient every 4 days; 3. reduce costs related to devices, staff employed. Conclusion Computerizing the preparation of anti-blastic drugs is a necessary path for the safety of the patient and all the operators involved, however it may be necessary to make changes in the preparation process to allow the software to work correctly. The comparison between pharmacist, clinician and, where necessary, the manufacturer of the drug, was effective in the preparation of this drug.

Septic epiphysitis and sequestrum formation in the glenoid of the scapula in a five-month-old foal diagnosed by computed tomography

2019 ◽  
Vol 7 (3) ◽  
pp. e000837
Author(s):  
Peter E Clements ◽  
Becky Jones ◽  
Richard Coomer
Keyword(s):  
Poor Prognosis ◽  
Serum Amyloid A ◽  
Proximal Humerus ◽  
Treatment Options ◽  
Elevated Serum ◽  
Acute Onset ◽  
Subchondral Bone Plate ◽  
Large Defect ◽  
Amyloid A ◽  
Bony Fragment

A five-month-old Connemara foal presented for acute-onset, severe left forelimb lameness with fever, neutrophilia and an elevated serum amyloid A concentration. Radiographs were suspicious of septic physitis of the proximal humerus. CT identified a large defect involving the central portion of the subchondral bone plate of the glenoid and a sequestered bony fragment within the defect, which were not seen radiographically. CT findings were consistent with septic epiphysitis and sequestrum formation, which had significant implications on available treatment options. The foal was given a poor prognosis for returning to soundness so was subject to humane euthanasia.

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