Immunological Aspects of Malignant Gliomas

AbstractGlioblastoma Multiforme (GBM) is the most common malignant primary brain neoplasm having a mean survival time of <24 months. This figure remains constant, despite significant progress in medical research and treatment. The lack of an efficient anti-tumor immune response and the micro-invasive nature of the glioma malignant cells have been explained by a multitude of immune-suppressive mechanisms, proven in different models. These immune-resistant capabilities of the tumor result in a complex interplay this tumor shares with the immune system. We present a short review on the immunology of GBM, discussing the different unique pathological and molecular features of GBM, current treatment modalities, the principles of cancer immunotherapy and the link between GBM and melanoma. Current knowledge on immunological features of GBM, as well as immunotherapy past and current clinical trials, is discussed in an attempt to broadly present the complex and formidable challenges posed by GBM.

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CD70 as a critical mediator of tumor progression and immunosuppression in gliomas.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.7_suppl.18 ◽

2017 ◽

Vol 35 (7_suppl) ◽

pp. 18-18

Author(s):

Changlin Yang ◽

Haitao Ge ◽

Linchun Jin ◽

Qiong J. Wang ◽

James C. Yang ◽

...

Keyword(s):

Tumor Progression ◽

T Regulatory Cells ◽

Malignant Gliomas ◽

Treatment Strategies ◽

Current Treatment ◽

Treatment Modalities ◽

Specific Cell ◽

Low Grade ◽

Chemokine Production ◽

Poor Survival Outcome

18 Background: For malignant gliomas, current treatment modalities are rarely curative, necessitating development of novel therapies. Cancer immunotherapy has represented one of the most promising new treatment strategies for patients with gliomas based on the evidence that patients with brain tumors are able to mount immune responses against the autologous tumors. However, very few tumor specific targets have been discovered in this malignancy. Thus, identifying clinical useful targets for immunotherapeutic approaches is desperately needed. Methods: CD70 expression was tested from primary GBM and low grade gliomas patient tissues. CD70 gene expression and clinical outcomes were culled from TCGA datasets. CD70 inducing CD8 T cells death was performed by flowcytometry. Results: We demonstrate that CD70, a member of the TNF ligand family, was constitutively overexpressed by primary IDH-wild-type LGG and GBMs with mesenchymal gene signatures. Elevated CD70 expression was also found in recurrent tumors and correlated with tumor progression and poor survival outcome in LGGs and GBMs. CD70 was shown to be directly involved in tumor-chemokine production and associated with sustained T regulatory cells in tumor. Importantly, CD70 played a role inducing CD8+T- specific cell death via engagement of the EREG-EGFR axis in glioma. Conclusions: CD70 is a multi-pronged modulator of immunosuppression in gliomas and enhances tumor progression.

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Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20102454 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2454 ◽

Cited By ~ 14

Author(s):

Nor Isnida Ismail ◽

Iekhsan Othman ◽

Faridah Abas ◽

Nordin H. Lajis ◽

Rakesh Naidu

Keyword(s):

Colorectal Cancer ◽

Side Effects ◽

Signaling Pathways ◽

Cancer Progression ◽

Current Knowledge ◽

Current Treatment ◽

Treatment Modalities ◽

Ancient Medicine ◽

Colorectal Cancer Progression ◽

Apoptosis Regulation

Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.

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Current Status of Knowledge and Awareness of Diabetes Mellitus in Saudi Arabia

Current Diabetes Reviews ◽

10.2174/1573399816999201012200841 ◽

2020 ◽

Vol 16 ◽

Author(s):

Asirvatham Alwin Robert ◽

Ahmad Dakeel Al Awad ◽

Mohamed Abdulaziz Al Dawish

Keyword(s):

Diabetes Mellitus ◽

Saudi Arabia ◽

Disease Risk ◽

Current Knowledge ◽

Adult Population ◽

Management Training ◽

Control Measures ◽

Current Status ◽

Treatment Modalities ◽

The Government

Abstract: Diabetes mellitus (DM) is a chronic disease, and the complications may be life-threatening; however, with proper treatment and control measures, it can be very well-managed. Self-management training and education of diabetes are critical in diabetes care and management. It is essential that patients with diabetes must have a comprehensive understanding of the nature of the disease, risk factors, complications, and possible treatment modalities to attenuate the complications. Over the last few years, DM in Saudi Arabia has been rapidly growing at an alarming rate. It has affected around one-fifth of the adult population, and by 2030, the numbers are predicted to rise further and exceed more than double the present number. An estimated tenfold increase has been reported over the past three decades in Saudi Arabia. However, there has not been much research focusing on understanding the knowledge and awareness of DM in Saudi Arabia as compared to developed nations. This review aims to present an overview of the current knowledge and awareness level of DM among the population of Saudi Arabia through an extensive review of the currently available literature. The review findings could be of immense assistance to the government, healthcare systems, educational institutions, and researchers to develop evidence-based programs, policies, and guidelines towards increasing the knowledge and awareness about diabetes and its management, so that early detection and management can be ensured to control the escalating burden of diabetes, in Saudi Arabia.

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The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200501235201 ◽

2020 ◽

Vol 15 (7) ◽

pp. 623-638

Author(s):

Saeideh Gholamzadeh Khoei ◽

Fateme Karimi Dermani ◽

Sara Malih ◽

Nashmin Fayazi ◽

Mohsen Sheykhhasan

Keyword(s):

Cardiovascular Disease ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Adult Stem Cells ◽

Heart Diseases ◽

Therapeutic Option ◽

Current Treatment ◽

Treatment Modalities ◽

Cellular Source

Background: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. Methods: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. Results: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. Conclusions: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

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Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Cancers ◽

10.3390/cancers13030451 ◽

2021 ◽

Vol 13 (3) ◽

pp. 451

Author(s):

Noemi Laprovitera ◽

Mattia Riefolo ◽

Elisa Ambrosini ◽

Christiane Klec ◽

Martin Pichler ◽

...

Keyword(s):

Current Knowledge ◽

Distant Metastases ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

Diagnostic Strategies ◽

Molecular Features ◽

Tissue Of Origin ◽

Novel Therapeutic Strategies ◽

Aggressive Clinical Behavior

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3–5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.

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Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

Journal of Clinical Medicine ◽

10.3390/jcm10061214 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1214

Author(s):

Ji Tu ◽

Jose Vargas Castillo ◽

Abhirup Das ◽

Ashish D. Diwan

Keyword(s):

Cervical Myelopathy ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Imaging Techniques ◽

Disease Process ◽

Classification Systems ◽

Molecular Features ◽

Formidable Challenge ◽

Long Term Treatment ◽

Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

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Infective Aortic Valve Endocarditis Causing Embolic Consecutive ST-Elevation Myocardial Infarctions

Case Reports in Cardiology ◽

10.1155/2019/2487616 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

Kanksha Peddi ◽

Alexander L. Hsu ◽

Tomas H. Ayala

Keyword(s):

Myocardial Infarction ◽

Infective Endocarditis ◽

Aortic Valve ◽

Index Case ◽

Current Treatment ◽

Myocardial Infarctions ◽

Treatment Modalities ◽

The Past ◽

First Case ◽

St Elevation

ST-elevation myocardial infarction (STEMI) is a rare and potentially fatal complication of infective endocarditis. We report the ninth case of embolic native aortic valve infective endocarditis causing STEMI and the first case to describe consecutive embolisms leading to infarctions of separate coronary territories. Through examination of this case in the context of the previous eight similar documented cases in the past, we find that infective endocarditis of the aortic valve can and frequently affect more than a single myocardial territory and can occur consecutively. Further, current treatment modalities for embolic infective endocarditis causing acute myocardial infarction are limited and unproven. This index case illustrates the potential severity of complications and the challenges in developing standardized management for such patients.

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Main Plant Extracts’ Active Properties Effective on Scopolamine-Induced Memory Loss

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317517715906 ◽

2017 ◽

Vol 32 (7) ◽

pp. 418-428 ◽

Cited By ~ 3

Author(s):

Ioana-Miruna Balmus ◽

Alin Ciobica

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Plant Extracts ◽

Current Knowledge ◽

Symptomatic Relief ◽

Memory Loss ◽

Current Treatment ◽

General Effect ◽

Function Loss ◽

Theory Research

Alzheimer’s disease leads to progressive cognitive function loss, which may impair both intellectual capacities and psychosocial aspects. Although the current knowledge points to a multifactorial character of Alzheimer’s disease, the most issued pathological hypothesis remains the cholinergic theory. The main animal model used in cholinergic theory research is the scopolamine-induced memory loss model. Although, in some cases, a temporary symptomatic relief can be obtained through targeting the cholinergic or glutamatergic neurotransmitter systems, no current treatment is able to stop or slow cognitive impairment. Many potentially successful therapies are often blocked by the blood–brain barrier since it exhibits permeability only for several classes of active molecules. However, the plant extracts’ active molecules are extremely diverse and heterogeneous regarding the biochemical structure. In this way, many active compounds constituting the recently tested plant extracts may exhibit the same general effect on acetylcholine pathway, but on different molecular ground, which can be successfully used in Alzheimer’s disease adjuvant therapy.

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Role of Vitamin D in the Prevention of Pancreatic Cancer

Journal of Nutrition and Metabolism ◽

10.1155/2010/721365 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Pubudu Bulathsinghala ◽

Kostas N. Syrigos ◽

Muhammad W. Saif

Keyword(s):

Pancreatic Cancer ◽

Vitamin D ◽

Dietary Intake ◽

Sun Exposure ◽

Current Treatment ◽

Treatment Modalities ◽

Hydroxyvitamin D ◽

Vitamin D Levels ◽

Advanced Stages

Pancreatic cancer is a malignancy of poor prognosis which is mostly diagnosed at advanced stages. Current treatment modalities are very limited creating great interest for novel preventive and therapeutic options. Vitamin D seems to have a protective effect against pancreatic cancer by participating in numerous proapoptotic, antiangiogenic, anti-inflammatory, prodifferentiating, and immunomodulating mechanisms. 25-hydroxyvitamin D [25(OH)D] serum concentrations are currently the best indicator of vitamin D status. There are three main sources of vitamin D: sun exposure, diet,and dietary supplements. Sun exposure has been associated with lower incidence of pancreatic cancer in ecological studies. Increased vitamin D levels seem to protect against pancreatic cancer, but caution is needed as excessive dietary intake may have opposite results. Future studies will verify the role of vitamin D in the prevention and therapy of pancreatic cancer and will lead to guidelines on adequate sun exposure and vitamin D dietary intake.

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