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https://www.readbyqxmd.com/read/28110462/endoluminal-and-interstitial-brachytherapy-for-the-treatment-of-gastrointestinal-malignancies-a-systematic-review
#1
REVIEW
Sujana Gottumukkala, Vasu Tumati, Brian Hrycushko, Michael Folkert
Radiation therapy is an integral component in the multimodality management of many gastrointestinal (GI) cancers at all stages of clinical presentation. With recent advances in technology and radiation delivery, external beam radiation therapy (EBRT) can be delivered with reduced toxicity. However, despite these advances, EBRT doses are still limited by the presence of radiosensitive serial structures near clinical targets in the GI tract. Relative to EBRT techniques, brachytherapy techniques have a lower integral dose and more rapid fall-off, allowing for high-dose delivery with little normal tissue exposure...
January 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28110457/reduced-proliferation-and-colony-formation-of-head-and-neck-squamous-cell-carcinoma-hnscc-after-dual-targeting-of-egfr-and-hedgehog-pathways
#2
Hannes Liebig, Georg Günther, Marlen Kolb, Christian Mozet, Andreas Boehm, Andreas Dietz, Gunnar Wichmann
PURPOSE: The hedgehog signalling pathway (Hh) is frequently active in head and neck squamous cell carcinoma (HNSCC). Overexpressed Hh associates with poor prognosis. The Hh inhibitor vismodegib targets smoothened, and based on molecular data, may prevent resistance to EGFR targeting. METHODS: To elucidate potential roles of vismodegib in HNSCC therapy, its sole effects and those combined with cisplatin, docetaxel, and cetuximab on HNSCC cell lines were assessed by MTT metabolisation and BrdU incorporation...
January 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28110453/update-on-the-diagnosis-and-treatment-of-cholangiocarcinoma
#3
REVIEW
Bryan Doherty, Vinod E Nambudiri, William C Palmer
PURPOSE OF REVIEW: Cholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes. Cholangiocarcinoma is subdivided into extrahepatic and intrahepatic variants. Intrahepatic cholangiocarcinoma is then further differentiated into (1) peripheral mass-forming tumors and (2) central periductal infiltrating tumors. We aimed to review the currently known risk factors, diagnostic tools, and treatment options, as well as highlight the need for further clinical trials and research to improve overall survival rates...
January 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/28110401/evaluating-the-utility-of-a-scoring-system-for-lipomas-of-the-cerebellopontine-angle
#4
Carlito Lagman, Brittany L Voth, Lawrance K Chung, Timothy T Bui, Seung J Lee, Natalie E Barnette, Quinton Gopen, Isaac Yang
BACKGROUND: Cerebellopontine angle (CPA) lipomas are rare, benign, slow-growing masses. Resections are considered in symptomatic patients who are refractory to targeted medical therapies, but at those stages the lipomas have often reached considerable sizes and encompass critical neurovascular structures. The objective of this study is to develop and to evaluate the utility of a scoring system for CPA lipomas. The hypothesis is that CPA lipomas with lower scores are probably best managed with early surgery...
January 21, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28110394/chimeric-antigen-receptor-car-t-cells-lessons-learned-from-targeting-of-cd19-in-b-cell-malignancies
#5
Kevin A Hay, Cameron J Turtle
Adoptive immunotherapy with chimeric antigen receptor-modified (CAR)-T cells is a rapidly growing therapeutic approach to treating patients with refractory cancer, with over 100 clinical trials in various malignancies in progress. The enthusiasm for CAR-T cells has been driven by the clinical success of CD19-targeted CAR-T cell therapy in B-cell acute lymphoblastic leukemia, and the promising data in B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Despite the success of targeting CD19 with CAR-T cells in early clinical studies, many challenges remain to improve outcomes, reduce toxicity, and determine the appropriate settings for CAR-T cell immunotherapy...
January 21, 2017: Drugs
https://www.readbyqxmd.com/read/28110393/nitric-oxide-production-in-the-striatum-and-cerebellum-of-a-rat-model-of-preterm-global-perinatal-asphyxia
#6
M Barkhuizen, W D J Van de Berg, J De Vente, C E Blanco, A W D Gavilanes, H W M Steinbusch
Encephalopathy due to perinatal asphyxia (PA) is a major cause of neonatal morbidity and mortality in the period around birth. Preterm infants are especially at risk for cognitive, attention and motor impairments. Therapy for this subgroup is limited to supportive care, and new targets are thus urgently needed. Post-asphyxic excitotoxicity is partially mediated by excessive nitric oxide (NO) release. The aims of this study were to determine the timing and distribution of nitric oxide (NO) production after global PA in brain areas involved in motor regulation and coordination...
January 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28110335/personalised-medicine-for-asthma-and-chronic-obstructive-pulmonary-disease
#7
Liam G Heaney, Lorcan P A McGarvey
Asthma and chronic obstructive pulmonary disease (COPD) are prevalent conditions, and despite recent advances and multiple available therapies and interventions, there remains a significant unmet clinical need. In recent years, it has become clear that there is both significant heterogeneity within each of these conditions and additionally significant overlap in many of the clinical and inflammatory features. In parallel, useful clinical and immunological biomarkers which inform about prognosis and response to therapy have emerged in both asthma and COPD...
January 21, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28110321/recent-advances-in-arsenic-trioxide-encapsulated-nanoparticles-as-drug-delivery-agents-to-solid-cancers
#8
Akhtar Anam, Wang Scarlet Xiaoyan, Ghali Lucy, Bell Celia, Wen Xuesong
Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28110300/irritable-bowel-syndrome-and-diet
#9
REVIEW
Piero Portincasa, Leonilde Bonfrate, Ornella de Bari, Anthony Lembo, Sarah Ballou
Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most commonly diagnosed gastrointestinal diseases. The impact of IBS on the general population is large due to its high prevalence, suboptimal medical treatments and significant economic burden. The pathophysiology of IBS is complex and treatments are often symptom-specific. The most common therapeutic approaches for IBS include education and reassurance, lifestyles (especially nutrition-based interventions), peripherally acting medications (which typically target motility), centrally acting medications (which target visceral hypersensitivity and pain) and psychological interventions (which aim to reduce the effects of stress or symptom-specific anxiety)...
January 20, 2017: Gastroenterology Report
https://www.readbyqxmd.com/read/28110220/hypoxia-inducing-factor-hif-1%C3%AE-derived-peptide-capable-of-inducing-cancer-reactive-cytotoxic-t-lymphocytes-from-hla-a24-patients-with-renal-cell-carcinoma
#10
Takafumi Minami, Naoki Matsumura, Koichi Sugimoto, Nobutaka Shimizu, Marco De Velasco, Masahiro Nozawa, Kazuhiro Yoshimura, Nanae Harashima, Mamoru Harada, Hirotsugu Uemura
Hypoxic tumor microenvironment makes cancer cells to be therapy-resistant and hypoxia-inducing factors (HIFs) play a central role in hypoxic adaptation. Especially, renal cell carcinoma (RCC) is often associated with von Hippel-Lindau (VHL) gene mutations, leading to up-regulation of HIFs. However, from a different point of view, this suggests the possibility that HIFs could be promising targets in anti-cancer therapy. In this study, we searched for HIF-1α-derived peptides that are able to induce RCC-reactive cytotoxic T lymphocytes (CTLs) from HLA-A24(+) RCC patients...
January 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28110184/structural-analysis-of-binding-functionality-of-folic-acid-peg-dendrimers-against-folate-receptor
#11
Diana Sampogna-Mireles, Ingrid D Araya-Durán, Valeria Márquez-Miranda, Jesús A Valencia-Gallegos, Fernando D González-Nilo
Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality...
January 6, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28110172/in%C3%A2-vivo-imaging-of-%C3%AE-galactosidase-stimulated-activity-in-hepatocellular-carcinoma-using-ligand-targeted-fluorescent-probe
#12
Eun-Joong Kim, Rajesh Kumar, Amit Sharma, Byungkwon Yoon, Hyun Min Kim, Hyunseung Lee, Kwan Soo Hong, Jong Seung Kim
Development of targeted, selective, and noninvasive fluorescent probes for in vivo visualization of tumor-associated overexpressed enzymes are highly anticipated for cancer diagnosis and therapy. Herein, we developed a noninvasive fluorescent probe (DCDHF-βgal) for the sensitive detection, and in vivo visualization of β-galactosidase in hepatocyte HepG2 cells and its xenograft model. As a model system for in vivo targeted imaging, DCDHF-βgal possessing galactose unit selectively target hepatocyte and monitor the β-galactosidase activity with deep tissue penetration, and low background interference...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28110069/peptide-and-nucleic-acid-directed-self-assembly-of-cationic-nanovehicles-through-giant-unilamellar-vesicle-modification-targetable-nanocomplexes-for-in-vivo-nucleic-acid-delivery
#13
A D Tagalakis, R Maeshima, C Yu-Wai-Man, J Meng, F Syed, L-P Wu, A M Aldossary, D McCarthy, S M Moghimi, S L Hart
: One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90-140 nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes...
January 18, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28109975/dna-damage-response-in-patients-with-pediatric-acute-lymphoid-leukemia-during-induction-therapy
#14
Júlia Plentz Portich, Rafael Pereira Dos Santos, Nathalia Kersting, Karolina Brochado Jorge, Pietro Rebelo Casagrande, Gabriela Dos Santos Costa, Jéssica Maria Gonçalves Dias Cionek, Danielly Brufatto Olguins, Marialva Sinigaglia, Franciele Faccio Busatto, Jenifer Saffi, Sharbel Weidner Maluf, Jiseh Fagundes Loss, Algemir Lunardi Brunetto, Rafael Roesler, Caroline Brunetto de Farias
Predicting the individual response to chemotherapy is a crucial challenge in cancer treatment. DNA damage caused by antitumor therapies evokes different repair mechanisms responses, such as Nucleotide Excision Repair (NER), whose components are being studied as prognosis biomarkers and target therapies. However, few reports have addressed DNA damages in pediatric Acute Lymphoid Leukemia (ALL). Hence, we conducted an observational follow-up study with pediatric patients to assess DNA damage (by Comet Assay) and gene expression from NER pathway during chemotherapy induction...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28109960/rna-nanoparticle-based-targeted-therapy-for-glioblastoma-through-inhibition-of-oncogenic-mir-21
#15
Tae Jin Lee, Ji Young Yoo, Dan Shu, Hui Li, Jianying Zhang, Jun-Ge Yu, Alena Cristina Jaime-Ramirez, Mario Acunzo, Giulia Romano, Ri Cui, Hui-Lung Sun, Zhenghua Luo, Matthew Old, Balveen Kaur, Peixuan Guo, Carlo M Croce
Targeted inhibition of oncogenic miRNA-21 has been proposed to treat glioblastoma by rescuing tumor suppressors, PTEN and PDCD4. However, systemic delivery of anti-miR-21 sequences requires a robust and efficient delivery platform to successfully inhibit this druggable target. Three-way-junction (3WJ)-based RNA nanoparticles (RNP), artificially derived from pRNA of bacteriophage phi29 DNA packaging motor, was recently shown to target glioblastoma. Here, we report that multi-valent folate (FA)-conjugated 3WJ RNP constructed to harbor anti-miR-21 LNA sequences (FA-3WJ-LNA-miR21) specifically targeted and delivered anti-miR-21 LNA and knocked down miR-21 expression in glioblastoma cells in vitro and in vivo with favorable biodistribution...
January 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28109959/crispr-cas9-mediated-genome-editing-as-a-therapeutic-approach-for-leber-congenital-amaurosis-10
#16
Guo-Xiang Ruan, Elizabeth Barry, Dan Yu, Michael Lukason, Seng H Cheng, Abraham Scaria
As the most common subtype of Leber congenital amaurosis (LCA), LCA10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. The most frequent mutation found in patients with LCA10 is a deep intronic mutation in CEP290 that generates a cryptic splice donor site. The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy. Here, we show that targeted genomic deletion using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system represents a promising therapeutic approach for the treatment of patients with LCA10 bearing the CEP290 splice mutation...
January 18, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28109945/discovery-of-a-series-of-n-5-quinolin-6-yl-pyridin-3-yl-benzenesulfonamides-as-pi3k-mtor-dual-inhibitors
#17
Jiankang Zhang, Xiaoqing Lv, Xiaodong Ma, Yongzhou Hu
Recently, the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been considered as promising targets for the treatment of cancer. Herein, we synthesized a series of N-(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as novel PI3K/mTOR dual inhibitors for cancer therapy. In the biological evaluation, compound 17e was identified as a potent PI3K/mTOR dual inhibitor, which significantly inhibit Class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level. Moreover, 17e display high potency against PC-3 cells (IC50 = 80 nM) in the anti-proliferative assay, and showed acceptable pharmacokinetic properties in vivo...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28109910/induction-of-neuroendocrine-differentiation-in-castration-resistant-prostate-cancer-cells-by-adipocyte-differentiation-related-protein-adrp-delivered-by-exosomes
#18
Li-Chiung Lin, Allen C Gao, Chih-Ho Lai, Jer-Tsong Hsieh, Ho Lin
Although overall mortality rate of prostate cancer (PCa) declines in recent years, castration-resistant prostate cancer (CRPC) remains incurable. Clinical evidence indicates that CRPC recurred from hormonal therapy exhibits neuroendocrine differentiated (NED) phenotypes, which could contribute to therapeutic resistance and poor survival. Understanding the onset of NED could lead us to develop new therapeutic strategies for CRPC. Although PCa is known as a lipid-enriched tumor, its role in CRPC development is not fully understood...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28109872/5-year-safety-and-efficacy-of-resolute%C3%A2-zotarolimus-eluting-stent-the-resolute-global-clinical-trial-program
#19
Robert W Yeh, Sigmund Silber, Lianglong Chen, Shaoliang Chen, Shirish Hiremath, Franz-Josef Neumann, Shubin Qiao, Shigeru Saito, Bo Xu, Yuejin Yang, Laura Mauri
OBJECTIVES: The authors evaluated the 5-year cumulative incidence of cardiovascular events following Resolute zotarolimus-eluting stent (R-ZES) implantation. BACKGROUND: Individual trials are often underpowered to show differences for low-frequency adverse events. The R-ZES was studied in 10 prospective clinical trials, designed with identical adverse event definitions, ascertainment, and adjudication. METHODS: The RESOLUTE Global Clinical Trial Program includes 7,618 patients treated with R-ZES: RESOLUTE first-in-human study (N = 139), RESOLUTE All Comers (N = 1,140), RESOLUTE International (N = 2,349), RESOLUTE US (N = 1,402), RESOLUTE US 38 mm (N = 114), RESOLUTE Japan (N = 100), RESOLUTE Japan Small Vessel Study (N = 65), RESOLUTE Asia (N = 311), RESOLUTE China Randomized Controlled Trial (N = 198), and RESOLUTE China Registry (N = 1,800)...
January 11, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28109822/extinction-of-relapsed-fear-does-not-require-the-basolateral-amygdala
#20
Nura W Lingawi, R Fredrick Westbrook, Vincent Laurent
It is well established that extinguished fears are restored with the passage of time or a change in physical context. These fear restoration phenomena are believed to mimic the conditions under which relapse occurs in patients that have been treated for anxiety disorders by means of cue-exposure therapy. Here, we used a rodent model to extinguish relapsed fear and assess whether this new extinction prevents further relapse. We found that activity in the basolateral amygdala (BLA) is required to initially extinguish conditioned fear, but this activity was not necessary to subsequently extinguish relapsed fear...
January 18, 2017: Neurobiology of Learning and Memory
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