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

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.

scholarly journals Immunological Aspects of Malignant Gliomas

2016 ◽  
Vol 43 (4) ◽  
pp. 494-502 ◽  
Author(s):  
Or Cohen-Inbar ◽  
Menashe Zaaroor
Keyword(s):  
Current Knowledge ◽  
Malignant Gliomas ◽  
Short Review ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Malignant Cells ◽  
Significant Progress ◽  
Complex Interplay ◽  
Mean Survival Time ◽  
Molecular Features

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.

scholarly journals GCT-23. MULTI-INSTITUTIONAL ANALYSIS OF TREATMENT MODALITIES IN BASAL GANGLIA AND THALAMIC GERMINOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii332-iii332
Author(s):  
Richard T Graham ◽  
Mohammad H Abu-Arja ◽  
Joseph Stanek ◽  
Ute Bartels ◽  
Andrea Cappellano ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Institutional Analysis ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Event Free Survival ◽  
Free Survival ◽  
Combine Chemotherapy ◽  
Imaging Characteristics ◽  
Significant Difference

Abstract BACKGROUND Central nervous system (CNS) germinomas are radiotherapy (RT)-sensitive tumors with excellent survival. Current treatment strategies combine chemotherapy with RT to reduce the field and dose of RT. There is no standard treatment for germinomas originating in the basal ganglia/thalami (BGTG) given their rarity and poorly-defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have been previously utilized; however, the optimal strategy remains unclear. METHODS Retrospective multi-institutional analysis was conducted across 18 institutions in four countries. RESULTS For 46 cases with non-metastatic BGTG, the event-free survival (EFS) was 86.9% at both 5 and 10 years, while overall survival (OS) was 100%, and 95.7% respectively at 5 and 10 years. Median RT dose and range for the various treatment volumes were as follows: CSI (n=10): 2340 cGy (1980–3060 cGy), WBI (n=8): 2340 (1800–3000 cGy), WVI (n=14): 2340 cGy (1800–2550 cGy), focal (n=9): 3600 cGy (3060–5400 cGy). There was no statistically significant difference in the EFS based on RT modality (p=0.57), but EFS for subjects with CSI and WBI were both 100%. The three subjects who received chemotherapy alone had significantly lower EFS than those who received chemotherapy and RT (p=0.001), but were salvageable with RT. CONCLUSION In the largest study to date for BGTG, there were no significant differences in outcomes between patients who received CSI, WBI, WVI or focal RT. This group of patients should be included in future prospective clinical trials, and a more limited RT field may be considered.

scholarly journals Immune Dysfunction and Multiple Treatment Modalities for the SARS-CoV-2 Pandemic: Races of Uncontrolled Running Sweat?

Biology ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 243
Author(s):  
Ashish Kothari ◽  
Vanya Singh ◽  
Uttam Kumar Nath ◽  
Sandeep Kumar ◽  
Vineeta Rai ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Performance ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Antigen Receptors ◽  
Multiple Treatment ◽  
Global Pandemic ◽  
Treatment Plans

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic threat with more than 11.8 million confirmed cases and more than 0.5 million deaths as of 3 July 2020. Given the lack of definitive pharmaceutical interventions against SARS-CoV-2, multiple therapeutic strategies and personal protective applications are being used to reduce the risk of high mortality and community spread of this infection. Currently, more than a hundred vaccines and/or alternative therapeutic regimens are in clinical trials, and some of them have shown promising results in improving the immune cell environment and controlling the infection. In this review, we discussed high-performance multi-directory strategies describing the uncontrolled deregulation of the host immune landscape associated with coronavirus disease (COVID-19) and treatment strategies using an anti-neoplastic regimen. We also followed selected current treatment plans and the most important on-going clinical trials and their respective outcomes for blocking SARS-CoV-2 pathogenesis through regenerative medicine, such as stem cell therapy, chimeric antigen receptors, natural killer (NK) cells, extracellular vesicular-based therapy, and others including immunomodulatory regimens, anti-neoplastic therapy, and current clinical vaccine therapy.

Tolerability of toceranib phosphate (Palladia) when used in conjunction with other therapies in 35 cats with feline oral squamous cell carcinoma: 2009–2013

2016 ◽  
Vol 19 (6) ◽  
pp. 568-575 ◽  
Author(s):  
Gina A Olmsted ◽  
John Farrelly ◽  
Gerald S Post ◽  
Jaclyn Smith
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Surgical Excision ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Low Grade ◽  
Treatment Delays ◽  
Gi Toxicity

Objectives Squamous cell carcinoma (SCC) is the most common oral tumor in cats and typically carries a poor prognosis with current treatment options. The objective of this study was to evaluate the toxicity of toceranib phosphate (Palladia; Pfizer) in cats with oral SCC in combination with other treatment modalities. Methods In this study, 35 cats were retrospectively evaluated to determine toxicity when treated with toceranib in combination with other treatment modalities. Cats received toceranib at a median dose of 2.75 mg/kg (range 1.9–4.17 mg/kg) 3 days a week. Cats also underwent additional therapies, including surgical excision, radiation therapy, chemotherapy and/or use of non-steroidal anti-inflammatory drugs. Results Toxicity was seen in six cats, with five cases of grade 1 or 2 gastrointestinal (GI) toxicity and one grade 4 metabolic toxicity. Toceranib was discontinued in one cat and two cats received dose reductions. None of the cats required treatment delays or hospitalization due to toxicity. Median toceranib treatment duration was 77 days (range 7–741 days). Conclusions and relevance This study revealed that toceranib was well tolerated by the majority of cats, with five cases of low-grade GI toxicity and one case of metabolic toxicity. Given the favorable toxicity profile, future studies further evaluating the safety and efficacy of toceranib for cats with oral SCC should be considered.

scholarly journals Perinatal Hypoxic-Ischemic Damage: Review of the Current Treatment Possibilities

2021 ◽  
pp. S379-S401
Author(s):  
A FRAJEWICKI ◽  
Z LAŠTŮVKA ◽  
V BORBÉLYOVÁ ◽  
S KHAN ◽  
K JANDOVÁ ◽  
...  
Keyword(s):  
Muscle Tone ◽  
Research Effort ◽  
Treatment Strategies ◽  
Perinatal Period ◽  
Current Treatment ◽  
Hypoxic Ischemic Encephalopathy ◽  
Treatment Modalities ◽  
Motor Disabilities ◽  
Promising Treatment ◽  
Ischemic Encephalopathy

Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxic-ischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.

scholarly journals ANGI-10. CHEMOTHERAPEUTIC STRESS INDUCES TRANSDIFFERENTIATION OF GLIOBLASTOMA CELLS TO PROMOTE VASCULAR MIMICRY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi32-vi32
Author(s):  
Shivani Baisiwala ◽  
Brenda Auffinger ◽  
Seamus Caragher ◽  
Jack Shireman ◽  
Riasat Ahsan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Current Standard ◽  
Tube Forming ◽  
Key Factor ◽  
Orthotopic Xenografts

Abstract Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor affecting adults, with a median survival of approximately 21 months after diagnosis. A key factor underlying the limited efficacy of current treatment modalities is the remarkable plasticity exhibited by GBM cells, which allows them to effectively adapt to changes induced by our current treatment strategies. In addition to their plasticity, GBM tumors are also highly vascularized with aberrant vessels that further promote its aggressiveness. Recent research has demonstrated that GBM cells have the ability to transdifferentiate into endothelial cells (ECs), which suggests that GBM cells may use their properties of plasticity and vascularity in concert, leading to the creation of tumor-derived blood vessels. The mechanism behind this transdifferentiation remains unclear. Here, we show that treatment with temozolamide (TMZ)-based chemotherapy (the current standard of care) induces time-dependent increases in expression of markers for glioma stem cells (GSCs) and immature and mature ECs over 8 days of treatment (p < .001) in multiple patient-derived xenograft (PDX) lines. In addition, GBM tumors growing as orthotopic xenografts in nude mice showed significantly increased expression of GSC markers (CD15 and CD133) and EC markers (CD105 and CD144) after 8 days of TMZ treatment (p < .01). Ex-vivo FACS analysis of these orthotopic xenografts showed the presence of immature and mature EC populations in addition to GSC populations. To assess the functionality of these increased EC populations, a tube forming assay was performed. Results showed that the tube forming capacity of PDX lines was significantly increased (p < .01) after therapy. Furthermore, immunofluorescence analysis revealed increased tumor-derived vessels in TMZ-recurrent tumors. Overall, this study identifies chemotherapeutic stress as a new driver of transdifferentiation of tumor cells to endothelial cells and highlights cellular plasticity as a key player in therapeutic resistance and tumor recurrence.

Pediatric Gliomas: Current Concepts on Diagnosis, Biology, and Clinical Management

2017 ◽  
Vol 35 (21) ◽  
pp. 2370-2377 ◽  
Author(s):  
Dominik Sturm ◽  
Stefan M. Pfister ◽  
David T.W. Jones
Keyword(s):  
Large Scale ◽  
Treatment Options ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Cns Tumors ◽  
Low Grade ◽  
Who Grade ◽  
Short Period ◽  
Life Threatening

Gliomas are the most common CNS tumors in children and adolescents, and they show an extremely broad range of clinical behavior. The majority of pediatric gliomas present as benign, slow-growing lesions classified as grade I or II by the WHO classification of CNS tumors. These pediatric low-grade gliomas (LGGs) are fundamentally different from IDH-mutant LGGs occurring in adults, because they rarely undergo malignant transformation and show excellent overall survival under current treatment strategies. However, a significant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classified as WHO grade III or IV high-grade gliomas (HGGs). Despite all therapeutic efforts, they remain largely incurable, with the most aggressive forms being lethal within months. Thus, the intentions of neurosurgeons, pediatric oncologists, and radiotherapists to improve care for pediatric patients with glioma range from increasing quality of life and preventing long-term sequelae in what is often a chronic, but rarely life-threatening disease (LGG), to uncovering effective treatment options to prolong patient survival in an almost universally fatal setting (HGG). The last decade has seen unprecedented progress in understanding the molecular biology underlying pediatric gliomas, fueling hopes to achieve both goals. Large-scale collaborative studies around the globe have cataloged genomic and epigenomic alterations in gliomas across ages, grades, and histologies. These studies have revealed biologic subgroups characterized by distinct molecular, pathologic, and clinical features, with clear relevance for patient management. In this review, we summarize hallmark discoveries that have expanded our knowledge in pediatric LGGs and HGGs, explain their role in tumor biology, and convey our current concepts on how these findings may be translated into novel therapeutic approaches.

Pediatric low grade focal brainstem glioma: outcomes of different treatment strategies and prognostic factors

2020 ◽  
Vol 16 (30) ◽  
pp. 2401-2410
Author(s):  
Caroline Elmaraghi ◽  
Mai K Bishr ◽  
Amr G Mousa ◽  
Soha Ahmed ◽  
Amal Refaat ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Treatment Modalities ◽  
Low Grade ◽  
Brain Stem Glioma ◽  
Tumor Site ◽  
Free Survival ◽  
Survival Differences

Background: This study explores the prognostic factors and outcomes of different treatment modalities in focal brain stem glioma (FBSG). Materials & methods: Pediatric FBSG patients diagnosed during 2010–2017 were retrospectively reviewed for clinical and therapeutic data. Results: A total of 71 cases were identified and the median age was 6.4 years. The 5-year overall- and progression-free survival were 74.5 and 70.6%, respectively. Radiotherapy was the main line of treatment (66.2%) and there were no survival differences between radiotherapy, chemotherapy and surveillance groups. Two independent poor prognostic factors were identified on multivariate analysis: age <8 years and cervicomedullary tumor site (p = 0.02 for both). Conclusion: Surveillance, radiotherapy and chemotherapy have comparable clinical outcomes in pediatric FBSG.

Current Treatment Strategies for Malignant Gliomas

2007 ◽  
Vol 00 (02) ◽  
pp. 98
Author(s):  
Michael Weller ◽  
Keyword(s):  
Malignant Gliomas ◽  
Treatment Strategies ◽  
Current Treatment

scholarly journals Treatment of Acute Pulmonary Embolism: Update on Newer Pharmacologic and Interventional Strategies

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Francesco Pelliccia ◽  
Michele Schiariti ◽  
Claudio Terzano ◽  
Abdul M. Keylani ◽  
Darrin C. D'Agostino ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Acute Pulmonary Embolism ◽  
Clinical Evidence ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Interventional Treatment ◽  
Common Complication ◽  
Treatment Paradigm ◽  
Institutional Experience

Acute pulmonary embolism (PE) is a common complication in hospitalized patients, spanning multiple patient populations and crossing various therapeutic disciplines. Current treatment paradigm in patients with massive PE mandates prompt risk stratification with aggressive therapeutic strategies. With the advent of endovascular technologies, various catheter-based thrombectomy and thrombolytic devices are available to treat patients with massive or submassive PE. In this paper, a variety of newer treatment strategies for PE are analyzed, with special emphasis on various interventional treatment strategies. Clinical evidence for utilizing endovascular treatment modalities, based on our institutional experience as well as a literature review, is provided.

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