scholarly journals Therapeutic Immunization against Glioblastoma

2018 ◽  
Vol 19 (9) ◽  
pp. 2540 ◽  
Author(s):  
Virgil Schijns ◽  
Chrystel Pretto ◽  
Anna Strik ◽  
Rianne Gloudemans-Rijkers ◽  
Laurent Deviller ◽  
...  
Keyword(s):  
Immune System ◽  
Brain Cancer ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Standard Of Care ◽  
The United States ◽  
Normal Brain ◽  
Dismal Prognosis ◽  
Medicinal Treatment ◽  
The Brain

Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient’s immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.

scholarly journals Making Sense of Current and Emerging Therapies in Pancreatic Cancer: Balancing Benefit and Value

2015 ◽  
pp. e222-e227 ◽  
Author(s):  
Daniel H. Ahn ◽  
Andrew H. Ko ◽  
Neal J. Meropol ◽  
Tanios S. Bekaii-Saab
Keyword(s):  
Pancreatic Cancer ◽  
Standard Of Care ◽  
The United States ◽  
Economic Effects ◽  
Making Sense ◽  
Dismal Prognosis ◽  
Emerging Therapies ◽  
Metastatic Setting ◽  
Localized Disease ◽  
New Treatments

Pancreatic cancer remains the fourth leading cause of cancer deaths in the United States with a dismal prognosis and a 5-year survival of less than 5% across all stages.1In 2014, there were approximately 46,420 new cases of pancreatic cancer with only 9% of patients having localized disease.2Given that the vast majority of patients present with advanced disease, much of the focus for drug development has been in the metastatic setting, which is evident with the advent of two combination chemotherapy regimens for this indication. Although conventional cytotoxic chemotherapy remains the standard of care, an ongoing search for novel therapeutic approaches continues. We will highlight several new approaches here, with a particular emphasis on immunotherapeutic strategies. We will also introduce concepts regarding the potential economic effects associated with the development and implementation of new treatments in pancreatic cancer.

scholarly journals Evolving Treatment of Advanced Urothelial Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 309-315 ◽  
Author(s):  
Srikala S. Sridhar
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Metastatic Disease ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Standard Of Care ◽  
The United States ◽  
Poor Performance Status ◽  
Cancer Of The Bladder

Urothelial cancer of the bladder is a smoking-related cancer and the fifth most common cancer in the United States. At presentation, up to 25% of patients will have muscle-invasive disease and, despite cystectomy or bladder-sparing trimodality approaches, will develop metastatic disease. Cisplatin-based combination chemotherapy regimens remain the standard of care in first-line metastatic disease. Although response rates to these regimens are high, they are rarely durable, and median overall survival is only 12 to 15 months. Treatment options following progression on cisplatin-based regimens or for patients unfit for cisplatin due to poor performance status, impaired renal function, or comorbidities have been quite limited. However, there is now a new class of drugs known as immune checkpoint inhibitors, which target the programmed cell death 1/programmed cell death-ligand 1 axis and promote antitumor immunity, that are showing both efficacy and tolerability. These drugs have now been approved for use in both cisplatin-treated and most recently cisplatin-unfit patients. Clinical trials are currently ongoing to determine how best to use these drugs and whether they should be used alone or in combination with other treatments. This review will discuss the current standard of care in the management of urothelial cancer and highlight recent trials of immunotherapy in this disease.

scholarly journals New Light on the Brain: The Role of Photosensitizing Agents and Laser Light in the Management of Invasive Intracranial Tumors

2003 ◽  
Vol 2 (4) ◽  
pp. 303-309 ◽  
Author(s):  
M. Sam Eljamel
Keyword(s):  
Brain Tissue ◽  
Malignant Gliomas ◽  
Surgical Excision ◽  
Normal Brain ◽  
Full Potential ◽  
Intracranial Tumors ◽  
Dismal Prognosis ◽  
Photosensitizing Agents ◽  
The Brain

Invasive intracranial tumors, particularly malignant gliomas, are very difficult to eradicate surgically and carry a dismal prognosis. The vast majority relapse locally indicating that their cure is dependent on radical and complete local excision. However, their ability to invade and hide among normal brain tissue, our inability to visualize and detect them, the low tolerance of brain tissue to ionizing radiation and the presence of the blood brain barrier are the main causes of our failure to eradicate them. Photodynamic detection with 100% specificity and more than 80% sensitivity offers an excellent chance of visualizing camouflaged tumor nests. Also, photodynamic therapy offers a very good chance of targeted destruction of the remaining tumor cells safely following surgical excision and may double the survival of patients harboring these awful tumors. More work needs to be done to refine this promising technology to exploit it to its full potential.

Brain metastases in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 326-326
Author(s):  
H. Alharbi ◽  
T. K. Choueiri ◽  
C. K. Kollmannsberger ◽  
S. North ◽  
M. J. MacKenzie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Local Treatment ◽  
Multivariable Analysis ◽  
First Line ◽  
The Brain

326 Background: Patients with brain metastases from advanced RCC treated in the targeted therapy era are not well characterized. Methods: Data from patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium from 6 centers. Results: One hundred six out of 705 (15%) patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-VEGF therapy and the rest developed metastases during follow-up. Of the patients with brain metastases, 6%, 68%, and 26% were in the favorable, intermediate and poor prognosis groups, respectively, per the Heng et al JCO 2009 criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 40% had a Karnofsky performance status (KPS) <80%, and 81% had symptoms of brain metastases. The median largest size and number of brain metastases was 1.8 cm (range 0.2–6.6) and 1 (range 1–20), respectively. Patients were treated with first-line sunitinib (n=77), sorafenib (n=23), bevacizumab (n=5), and temsirolimus (n=1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). The brain metastases of 59 patients were evaluable and based on the local treatment and/or targeted therapy achieved 7 (12%) complete responses, 23 (39%) partial responses, 14 (24%) patients with stable disease, and 15 (25%) patients with progressive disease in the brain metastases. Patients with more than 4 brain metastases vs. those with no more than 4 have an overall survival time from diagnosis of brain metastasis of 3.9 vs. 15.4 months (p=0.0051). Previous nephrectomy, sarcomatoid, and non-clear cell histology are not associated with development of brain metastases. On multivariable analysis, KPS<80% (p=0.0139), diagnosis to treatment with targeted therapy <1 year (p=0.0012), and higher number of brain metastases (p=0.0311) were associated with worse survival from diagnosis of brain metastases. Conclusions: In patients with brain metastases from RCC, KPS at start of therapy, diagnosis to treatment time and number of brain metastases may be prognostic factors for overall survival. [Table: see text]

scholarly journals Repression of RNA message for F-box proteins in the tumors of patients with glioblastoma.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Brain Cancer ◽  
Gene Expression Analysis ◽  
Normal Brain ◽  
Significant Differential Expression ◽  
Differential Gene Expression Analysis ◽  
Genes Encoding ◽  
Differential Gene ◽  
The Brain ◽  
Median Survival Rate

Glioblastoma is the most common brain cancer in adults and has a 15 month median survival rate (1, 2). We performed differential gene expression analysis, comparing the glioblastoma transcriptome from 17 patients to the transcriptome of 8 non-affected, “normal” brain samples using a published dataset (3). Three separate genes encoding F-box proteins (4), including FBXW7, FBXO41, and FBXL16 were differentially expressed and at significantly lower levels in the tumors of patients with glioblastoma than in the brain. Significant differential expression of FBXW7, FBXO41 and FBXL16 was also observed in glioblastomas from the REMBRANDT study (5).

scholarly journals De Novo A-to-I RNA Editing Discovery in lncRNA

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2959
Author(s):  
Domenico Alessandro Silvestris ◽  
Chiara Scopa ◽  
Sara Hanchi ◽  
Franco Locatelli ◽  
Angela Gallo
Keyword(s):  
Rna Editing ◽  
Brain Cancer ◽  
Brain Cortex ◽  
De Novo ◽  
Large Fraction ◽  
Bioinformatic Analysis ◽  
Normal Brain ◽  
Editing Event ◽  
Non Coding Rnas ◽  
The Brain

Background: Adenosine to inosine (A-to-I) RNA editing is the most frequent editing event in humans. It converts adenosine to inosine in double-stranded RNA regions (in coding and non-coding RNAs) through the action of the adenosine deaminase acting on RNA (ADAR) enzymes. Long non-coding RNAs, particularly abundant in the brain, account for a large fraction of the human transcriptome, and their important regulatory role is becoming progressively evident in both normal and transformed cells. Results: Herein, we present a bioinformatic analysis to generate a comprehensive inosinome picture in long non-coding RNAs (lncRNAs), using an ad hoc index and searching for de novo editing events in the normal brain cortex as well as in glioblastoma, a highly aggressive human brain cancer. We discovered >10,000 new sites and 335 novel lncRNAs that undergo editing, never reported before. We found a generalized downregulation of editing at multiple lncRNA sites in glioblastoma samples when compared to the normal brain cortex. Conclusion: Overall, our study discloses a novel layer of complexity that controls lncRNAs in the brain and brain cancer.

Everolimus for patients with metastatic renal cell carcinoma (mRCC) refractory to anti-VEGF therapy: Preliminary results of a pooled analysis of noninterventional studies.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 392-392
Author(s):  
Laurence Albiges ◽  
Lothar Bergmann ◽  
Jean-Christophe Eymard ◽  
Manuela Schmidinger ◽  
Aristotelis Bamias ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Standard Of Care ◽  
Pooled Analysis ◽  
Similar Proportion ◽  
Prospective Data ◽  
Preliminary Results ◽  
Anti Vegf ◽  
Risk Prognosis ◽  
Health Deterioration

392 Background: In RECORD-1, the oral mTOR inhibitoreverolimus significantly improved PFS compared with placebo in patients with mRCC refractory to 1 or 2 prior VEGFr-TKIs. Here, we provide prospective data from European countries on everolimus use in patients with mRCC after failure of anti-VEGF therapy. Methods: To evaluate the safety and efficacy of everolimus in routine clinical practice, data were pooled from 4 prospective, noninterventional studies conducted in Germany, France, Greece, and Austria. Results: Data from the first 6 months of treatment are available for 534 patients. At baseline, median time since diagnosis of first metastasis from RCC was 1.8 years, and 91% of patients were of favorable or intermediate MSKCC risk prognosis. Predominantly clear cell mRCC was evident in 90% of patients, and most patients had prior nephrectomy (89%). Best overall response by investigator assessment was partial response in 13%, stable disease in 56%, and progressive disease in 32%. Overall, 77% of patients experienced ≥1 adverse event (AE) and 22% experienced ≥1 serious AE. AEs occurring in >5% of patients included stomatitis (25%), anemia (13%), asthenia (9%), fatigue (8%), pneumonitis (8%), rash (8%), diarrhea (7%), decreased appetite (7%), hypertriglyceridemia (6%), dyspnea (6%), nausea (6%), and peripheral edema (5%). Serious AEs occurring in >2% of patients included stomatitis (3.4%), general health deterioration (2.2%), anemia (2.1%), dyspnea (2.1%), and pneumonitis (2.1%). Median everolimus duration was 4.8 months. Treatment was discontinued due to disease progression in 50% of patients and AEs in 24% of patients. A similar proportion of patients had Karnofsky performance status ≥70 at baseline (86%) and at end of analysis (80%). Updated data will be available in February 2012. Conclusions: Preliminary results of this pooled analysis of 4 European studies substantiate the safety of everolimus reported in the pivotal RECORD-1 trial and provide evidence for the effectiveness of everolimus in routine use. The results support the use of everolimus as a standard of care for VEGF-refractory patients with mRCC.

scholarly journals A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Odette Leiter ◽  
Gerd Kempermann ◽  
Tara L. Walker
Keyword(s):  
Immune System ◽  
Adult Neurogenesis ◽  
Immune Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Intrinsic Cues ◽  
Normal Brain Function ◽  
The Brain

Immune regulation of the brain is generally studied in the context of injury or disease. Less is known about how the immune system regulates the brain during normal brain function. Recent work has redefined the field of neuroimmunology and, as long as their recruitment and activation are well regulated, immune cells are now known to have protective properties within the central nervous system in maintaining brain health. Adult neurogenesis, the process of new neuron generation in the adult brain, is highly plastic and regulated by diverse extrinsic and intrinsic cues. Emerging research has shown that immune cells and their secreted factors can influence adult neurogenesis, both under baseline conditions and during conditions known to change neurogenesis levels, such as aging and learning in an enriched environment. This review will discuss how, under nonpathological conditions, the immune system can interact with the neural stem cells to regulate adult neurogenesis with particular focus on the hippocampus—a region crucial for learning and memory.

scholarly journals CALCULATION OF BNCT DOSIMETRY FOR BRAIN CANCER BASED ON KARTINI RESEARCH REACTOR USING PHITS CODE

2017 ◽  
Vol 19 (3) ◽  
pp. 159
Author(s):  
Suhendra Gunawan Ntoy ◽  
Yohannes Sardjono
Keyword(s):  
Glioblastoma Multiforme ◽  
Dose Rate ◽  
Brain Cancer ◽  
Treatment Time ◽  
Absorbed Dose ◽  
Absorbed Dose Rate ◽  
Boron Neutron Capture ◽  
Dismal Prognosis ◽  
Irradiation Geometry ◽  
The Brain

Cancer is a dangerous disease caused by the growth of a mass of cells that are unnatural and uncontrollable. Glioblastoma, also called as glioblastoma multiforme (GBM), is one of dangerous brain cancer. The dismal prognosis associated with glioblastoma is attributable not only to its aggressive and infiltrative behavior, but also to its location typically deep in the parenchyma of the brain. In resolving this chalenge, the BNCT method can be a solution. This study aims to calculate BNCT dosimetry in different of cancer positions and irradiation geometries using PHITS code. The results show that the deeper the cancers target at brain the slower the total absorbed dose rate of cancer target. It takes a longer treatment time. Based on the treatment time and total absorbed dose rate of cancer target, the TOP irradiation geometry is an appropriate choice in treating the cancer target in this case. To achieve the histopathological cure of GBM at the primary site, the absorbed dose of brain was calculated to be 1.07 Gy and 1.64 Gy for the LLAT and PA irradiation geometry, respectively. While, for cancer position of 3 cm, 5 cm, 7.15 cm, 9 cm, and 11 cm, the absorbed dose of brain is 0.25 Gy, 0.48 Gy, 0.85 Gy, 1.33 Gy, and 2.01 Gy, respectively. In addition to the stochastic effect, it was found also deterministic effects that may be produced such as cataracts.Keywords: BNCT dosimetry; GBM; brain cancer cases; PHITS; MIRD phantom PERHITUNGAN DOSIMETRI BNCT PADA KANKER OTAK BERBASIS REAKTOR RISET KARTINI MENGGUNAKAN PROGRAM PHITS. Kanker merupakansalahsatu penyakit berbahaya yang diakibatkan oleh tumbuhnya sekumpulan massa sel-sel yang tidak wajar dan tidak terkendali. Salah satu penyakit kanker otak yang berbahaya adalah Glioblastoma atau yang biasa disebut Glioblastoma Multiforme (GBM). Prognosis suram terkait dengan GBM tidak hanya untuk perilaku agresif dan infiltrasi, tetapi juga terhadaplokasi yang jauh di dalam parenkim otak. Untuk menjawab hal tersebut, Boron Neutron Capture Therapy (BNCT) dapat menjadi solusi. Penilitian ini bertujuan untuk menghitung dosimetri BNCT dalam berbagai posisikan kerdan geometri penyinaran dengan menggunakan program PHITS. Hasil perhitungan menunjukkan bahwa semakin dalam target kanker di otak maka semakin kecil total laju dosis serap dari target kanker. Semakin dalam target kanker di otak dibutuhkan waktu pengobatan yang semakin lama. Berdasarkan waktu pengobatan dan laju dosis serap dari target kanker, bidang penyinaran TOP merupakan pilihan yang tepat dalam mengobati target kanker dalam kasus ini. Untuk mencapai penyembuhan GBM secara histopatologis di lokasi utama, dosis serap dari otak dihitung berturut-turut sebesar 1,07 Gy dan 1,64 Gy untuk bidang penyinaran LLAT dan PA. Sedangkan, untuk posisi kanker 3 cm, 5 cm, 7,15 cm, 9 cm, dan 11 cm, berturut-turut dosis serap dari otak adalah 0,25 Gy, 0,48 Gy, 0,85 Gy, 1,33 Gy, and 2,01 Gy. Selain adanya efek stokastik, ditemukan juga efek deterministik yang mungkin dihasilkan seperti katarak.Kata kunci: Dosimetri BNCT, GBM, kasuskankerotak, geometripenyinaran, posisikanker, ORNLMIRD phantom.

scholarly journals Pediatric Brain Tumors Diagnosis and Treatment

2021 ◽  
pp. 315-352
Author(s):  
Elena Locci ◽  
Silvia Raymond
Keyword(s):  
Radiation Therapy ◽  
Cognitive Function ◽  
Brain Cancer ◽  
Young Patients ◽  
Standard Of Care ◽  
Pediatric Brain Tumors ◽  
Keywords Cancer ◽  
Pediatric Brain ◽  
The Brain ◽  
Cancer In Children

Meduloblastoma is a rare but devastating brain cancer in children. The cancer can spread through the spinal fluid and deposit elsewhere in the brain or spine. Radiation therapy to the whole brain and spine, followed by an extra dose of radiation to the back of the brain, prevented this spread and became the standard of care. However, radiation used to treat such tumors causes damage to the brain and impairs cognitive function. It affects, especially in young patients whose brains are growing. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

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