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radiation BBB

Daniel Coluccia, Carlyn A Figueiredo, Megan YiJun Wu, Alexandra N Riemenschneider, Roberto Diaz, Amanda Luck, Christian Smith, Sunit Das, Cameron Ackerley, Meaghan O'Reilly, Kullervo Hynynen, James T Rutka
Glioblastoma (GBM) is the most common and aggressive primary brain tumor resulting in high rates of morbidity and mortality. A strategy to increase the efficacy of available drugs and enhance the delivery of chemotherapeutics through the blood brain barrier (BBB) is desperately needed. We investigated the potential of Cisplatin conjugated gold nanoparticles (GNP-UP-Cis) in combination with MR-guided Focused Ultrasound (MRgFUS) to intensify GBM treatment. Viability assays demonstrated that GNP-UP-Cis greatly inhibits the growth of GBM cells compared to free cisplatin and shows marked synergy with radiation therapy...
February 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Jothilingam Sivapackiam, Richard Laforest, Vijay Sharma
INTRODUCTION: 68 Ga-Galmydar is an avid transport substrate of ABCB1 (P-Glycoprotein; 170kDa plasma membrane protein), breast cancer resistance protein (BCRP; ABCG2; 72kDa), penetrates human epidermal carcinoma (KB3-1), breast cancer (MCF7), embryonic kidney (HEK 293) tumor cells and rat cardiomyoblasts, and localizes within the mitochondria of tumor and myocardium cells. 68 Ga-Galmydar excretes from blood pool quickly, and shows stable retention within rat myocardium in vivo for extended periods, therefore, the agent shows potential to enable myocardial perfusion imaging...
December 1, 2017: Nuclear Medicine and Biology
Rodica Di Lorenzo, Manmeet S Ahluwalia
Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities...
December 2017: Therapeutic Advances in Medical Oncology
Xue Li, Yingchun Wang, Jia Wang, Tianwei Zhang, Li Zheng, Zhenfan Yang, Ligang Xing, Jinming Yu
The prognosis of patients with brain metastasis (BM) is poor. In our study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC. Besides, the antitumor activity displayed no difference between radiation concurrently with AZD3759 and radiation sequentially with AZD3759. Mechanistically, we found that two factors determined the enhanced efficacy: cells with EGFRm which were sensitive to AZD3759, and a relative high concentration of AZD3759...
February 12, 2018: International Journal of Cancer. Journal International du Cancer
Habib Baghirov, Sofie Snipstad, Einar Sulheim, Sigrid Berg, Rune Hansen, Frits Thorsen, Yrr Mørch, Catharina de Lange Davies, Andreas K O Åslund
The treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1...
2018: PloS One
Oxana Semyachkina-Glushkovskaya, Jürgen Kurths, Ekaterina Borisova, Sergei Sokolovski, Vanya Mantareva, Ivan Angelov, Alexander Shirokov, Nikita Navolokin, Natalia Shushunova, Alexander Khorovodov, Maria Ulanova, Madina Sagatova, Ilana Agranivich, Olga Sindeeva, Artem Gekalyuk, Anastasiya Bodrova, Edik Rafailov
Photodynamic treatment (PDT) causes a significant increase in the permeability of the blood-brain barrier (BBB) in healthy mice. Using different doses of laser radiation (635 nm, 10-40 J/cm2 ) and photosensitizer (5-aminolevulinic acid - 5-ALA, 20 and 80 mg/kg, i.v.), we found that the optimal PDT for the reversible opening of the BBB is 15 J/cm2 and 5-ALA, 20 mg/kg, exhibiting brain tissues recovery 3 days after PDT. Further increases in the laser radiation or 5-ALA doses have no amplifying effect on the BBB permeability, but are associated with severe damage of brain tissues...
November 1, 2017: Biomedical Optics Express
Anna Lisa Iorio, Martina da Ros, Lorenzo Genitori, Maurizio Lucchesi, Fabiana Colelli, Giacomo Signorino, Francesco Cardile, Giacomo Laffi, Maurizio de Martino, Claudio Pisano, Iacopo Sardi
Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months. Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ. The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy...
October 27, 2017: Oncotarget
Jung Seok Kim, Dae Hwan Shin, Jin-Seok Kim
Glioblastoma stem cells (GSCs), which are identified as subpopulation of CD133+ /ALDH1+ , are known to show resistance to the most of chemotherapy and radiation therapy, leading to the recurrence of tumor in glioblastoma multiforme (GBM) patients. Also, delivery of temozolomide (TMZ), a mainline treatment of GBM, to the GBM site is hampered by various barriers including the blood-brain barrier (BBB). A dual-targeting immunoliposome encapsulating TMZ (Dual-LP-TMZ) was developed by using angiopep-2 (An2) and anti-CD133 monoclonal antibody (CD133 mAb) for BBB transcytosis and specific delivery to GSCs, respectively...
January 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Elias J Sayour, Duane A Mitchell
Malignant brain tumors are the most common cause of solid cancer death in children. New targeted therapies are vital to improve treatment outcomes, but must be developed to enable trafficking across the blood brain barrier (BBB). Since activated T cells cross the BBB, cancer immunotherapy can be harnessed to unlock the cytotoxic potential of the immune system. However, standard of care treatments (i.e., chemotherapy and radiation) applied concomitant to pediatric brain tumor immunotherapy may abrogate induction of immunotherapeutic responses...
October 21, 2017: Brain Sciences
J M Castañeda-Gill, A P Ranjan, J K Vishwanatha
Glioblastoma (GBM) is an aggressive, grade IV brain tumor that develops from astrocytes located within the cerebrum, resulting in poor prognosis and survival rates following an accepted treatment regimen of surgery, radiation, and temozolomide. Thus, development of new therapeutics is necessary. During the last two decades, methylene blue (MB) has received increased attention as a potential neurotherapeutic due to its duality in brain cancers and neurodegenerative diseases. While MB is capable of easily permeating the blood-brain barrier, its therapeutic concentrations in GBM are known to induce off-target cytotoxicity and thus, another mode of drug delivery must be considered...
August 2017: Journal of Nanomedicine & Nanotechnology
Sukanya Bhunia, Venugopal Vangala, Dwaipayan Bhattacharya, Halley Gora Ravuri, Madhusudana Kuncha, Sumana Chakravarty, Ramakrishna Sistla, Arabinda Chaudhuri
Despite significant progress in neurosurgery and radiation therapy during the past decade, overall survivability (OS) of glioblastoma patients continues to be less than 2 years. The scope of systemic chemotherapy is greatly limited by poor drug transport across the blood brain barrier (BBB) and, thereby, suboptimal drug accumulation in glioma tissue. To this end, use of large amino acid transporter-1 (LAT1) overexpressed both on brain capillary endothelial cells (BCECs) and glioma cells has begun. Prior reports on the use of LAT1 mediated delivery of model drugs showed their brain accumulations...
November 6, 2017: Molecular Pharmaceutics
Xin Zhang, Ran Xu, Chao Zhang, Yangyang Xu, Mingzhi Han, Bin Huang, Anjing Chen, Chen Qiu, Frits Thorsen, Lars Prestegarden, Rolf Bjerkvig, Jian Wang, Xingang Li
BACKGROUND: Resistance to adjuvant radiotherapy is a major cause of treatment failure in patients with glioblastoma (GBM). Autophagy inhibitors have been shown to enhance the efficacy of radiotherapy for certain solid tumors. However, current inhibitors do not penetrate the blood-brain-barrier (BBB). Here, we assessed the radiosensitivity effects of the antipsychotic drug trifluoperazine (TFP) on GBM in vitro and in vivo. METHODS: U251 and U87 GBM cell lines as well as GBM cells from a primary human biopsy (P3), were used in vitro and in vivo to evaluate the efficacy of TFP treatment...
September 5, 2017: Journal of Experimental & Clinical Cancer Research: CR
Chee-Seng Tan, Byoung Chul Cho, Ross A Soo
With the use of EGFR TKIs, patient survival is now prolonged and as a consequence, a higher chance of development of CNS metastases has been observed during the course of the disease. CNS metastases remains a therapeutically challenging subset of patient to treat owing to the blood-brain barrier (BBB). Prior to routine EGFR mutation testing, surgical resection, stereotactic radiosurgery and/or whole brain radiation therapy (WBRT) were the main treatment options whereas treatment options for patients with leptomeningeal metastases (LM) included intra-thecal chemotherapy, WBRT, and ventriculo-peritoneal shunting...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Anirudh Sattiraju, Xiaobing Xiong, Darpan N Pandya, Thaddeus J Wadas, Ang Xuan, Yao Sun, Youngkyoo Jung, Kiran Kumar Solingapuram Sai, Jay F Dorsey, King C Li, Akiva Mintz
Glioblastoma (GBM) is the most common primary malignant astrocytoma characterized by extensive invasion, angiogenesis, hypoxia, and micrometastasis. Despite the relatively leaky nature of GBM blood vessels, effective delivery of antitumor therapeutics has been a major challenge due to the complications caused by the blood-brain barrier (BBB) and the highly torturous nature of newly formed tumor vasculature (blood tumor barrier-BTB). External beam radiotherapy was previously shown to be an effective means of permeabilizing central nervous system (CNS) barriers...
October 2017: Molecular Cancer Therapeutics
Marie Kalm, Martina Boström, Åsa Sandelius, Yohanna Eriksson, C Joakim Ek, Kaj Blennow, Thomas Björk-Eriksson, Henrik Zetterberg
A blood biomarker to monitor individual susceptibility to neuronal injury from cranial radiotherapy could potentially help to individualize radiation treatment and thereby reduce the incidence and severity of late effects. An important feature of such a blood biomarker is that its concentration is not confounded by varying degrees of release from the brain into the blood across the blood-brain barrier (BBB). In this study, we investigated serum neurofilament light protein (NFL) concentrations in 21-day old mice following a single dose of cranial irradiation (8 Gy)...
May 15, 2017: Brain Research
Jian-Zhong Hu, Xiao-Kai Wang, Yong Cao, Dong-Zhe Li, Tian-Ding Wu, Tao Zhang, Da-Qi Xu, Hong-Bin Lu
BACKGROUND: Spinal cord injury (SCI) is a major public health issue that leads to neurological dysfunctions and morbidities in patients. Tetramethylpyrazine (TMP) plays a neuroprotective role in SCI; however, the underlying mechanism has not been fully elucidated. Objective In the present study, we aimed to investigate the mechanisms and therapeutic effects of TMP on SCI. METHODS: A contusion SCI model was established that used a modified Allen's method. In the TMP group, TMP (200 mg/kg) was injected daily for 5 days post-injury, while in the Negative Control (NC) group, an equal volume of normal saline was injected...
March 13, 2017: Current Neurovascular Research
Claudia Proto, Martina Imbimbo, Rosaria Gallucci, Angela Brissa, Diego Signorelli, Milena Vitali, Marianna Macerelli, Giulia Corrao, Monica Ganzinelli, Francesca Gabriella Greco, Marina Chiara Garassino, Giuseppe Lo Russo
Lung cancer is one of the major causes of cancer related mortality worldwide. Brain metastases (BM) complicate clinical evolution of non-small cell lung cancer (NSCLC) in approximately 25-40% of cases, adversely influencing quality of life (QoL) and overall survival (OS). Systemic therapy remains the standard strategy for metastatic disease. Nevertheless, the blood-brain barrier (BBB) makes central nervous system (CNS) a sanctuary site. To date, the combination of chemotherapy with whole brain radiation therapy (WBRT), surgery and/or stereotactic radiosurgery (SRS) represents the most used treatment for patients (pts) with intracranial involvement...
December 2016: Translational Lung Cancer Research
Hongmei Liu, Yandong Xie, Yafei Zhang, Yifan Cai, Baiyang Li, Honglin Mao, Yingguo Liu, Jun Lu, Longzhen Zhang, Rutong Yu
The treatment of malignant primary brain tumors is challenging. Concomitant radiochemotherapy has become the standard clinical treatment for malignant glioma, but there are two critical challenges to overcome in order to increase efficacy. First, glioma is known to have increased resistant to radiation due to its intra-tumoral hypoxia. In addition, the blood-brain barrier (BBB) restricts the distribution of the chemotherapeutic agent to the brain. Therefore, we developed a hypoxic radiosensitizer-prodrug liposome (MLP), in order to deliver DOX to the tumor and to overcome the above challenges, achieving a synergistic chemo-/radiotherapy treatment of malignant glioma...
March 2017: Biomaterials
Analiz Rodriguez, Stephen B Tatter
Recurrent malignant glioma continues to be a clinical challenge, and repeat surgery is an option in only select patients. Stereotactic laser ablation, a new minimally invasive technique, can be used as an alternative to surgery. We review the current literature on laser ablation for recurrent malignant gliomas as well as discuss practical and theoretical advantages and disadvantages of this emerging technique in comparison with repeat surgery or radiation. We also discuss the potential for laser ablation to augment adjuvant therapies, namely, chemotherapy, radiation, and immunotherapy...
December 2016: Neurosurgery
Ian Lee, Steven Kalkanis, Constantinos G Hadjipanayis
BACKGROUND: The value of maximal safe cytoreductive surgery in recurrent high-grade gliomas (HGGs) is gaining wider acceptance. However, patients may harbor recurrent tumors that may be difficult to access with open surgery. Laser interstitial thermal therapy (LITT) is emerging as a technique for treating a variety of brain pathologies, including primary and metastatic tumors, radiation necrosis, and epilepsy. OBJECTIVE: To review the role of LITT in the treatment of recurrent HGGs, for which current treatments have limited efficacy, and to discuss the possible role of LITT in the disruption of the blood-brain barrier to increase delivery of chemotherapy locoregionally...
December 2016: Neurosurgery
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