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Precision therapy

Massimo Del Fabbro, Stefano Corbella, Patrick Sequeira-Byron, Igor Tsesis, Eyal Rosen, Alessandra Lolato, Silvio Taschieri
BACKGROUND: When primary root canal therapy fails, periapical lesions can be retreated with or without surgery. Root canal retreatment is a non-surgical procedure that involves removal of root canal filling materials from the tooth, followed by cleaning, shaping and obturating of the canals. Root-end resection is a surgical procedure that involves exposure of the periapical lesion through an osteotomy, surgical removal of the lesion, removal of part of the root-end tip, disinfection and, commonly, retrograde sealing or filling of the apical portion of the remaining root canal...
October 19, 2016: Cochrane Database of Systematic Reviews
Stefan Holdenrieder
Liquid profiling is a traditional concept in laboratory diagnostics using patterns of blood-derived biochemical molecules for disease detection and characterization. Beyond protein and cellular parameters, molecular biomarkers at the DNA, RNA and miRNA level have been developed as promising diagnostic tools in metabolic and malignant diseases as new technologies for ultrasensitive profiling of nucleic acids in blood and body fluids became available. In cancer disease, they are successfully applied for the stratification of patients for individually tailored therapies, treatment monitoring and the sensitive detection of minimal residual disease...
2016: Advances in Experimental Medicine and Biology
Jeganathan Manivannan, Manjunath Prashanth, Venkatesan Saravana Kumar, Manickaraj Shairam, Jayachandran Subburaj
Since there is no precise therapy for treating vascular calcification by directly targeting the vascular wall, we aim to unveil novel drug targets through mining the molecular effect of a high phosphate environment on vascular cells through computational methods. Here, we hypothesize that manipulation of the vascular pathogenic network by small molecule therapeutics predicted from prior knowledge might offer great promise. With this, we intend to understand the publicly available transcriptomic data of vascular smooth muscle cells and endothelial cells exposed to the high phosphate induced vascular calcification milieu and to re-examine the above published experiments for reasons different from those examined in the previous studies through multilevel systems biological understanding...
October 18, 2016: Molecular BioSystems
Vina Pulido, Shin Yin Lee, Naomi Yu Ko
In the era of precision medicine and targeted therapy, diagnostic inaccuracy can have tremendous ramifications. We present the case of a 61-year-old man initially diagnosed with small cell lung cancer by pathology. Prior to initiating chemotherapy, multidisciplinary discussions led to an amendment of the diagnosis to medullary thyroid cancer.
May 2016: Case Reports in Oncology
Boriphat Methachan, Kamolrat Thanapprapasr
The emergence of theranostics with ultrasound technology is a promising development, as it opens pathways to providing more effective treatments for cancer. Advancements in ultrasound imaging would give a more detailed and accurate image for better diagnosis and treatment planning. Polymeric ultrasound contrast agents (UCAs) are appealing because they are stable and easily modified for active targeting. In addition, a better therapy could be achieved in conjunction with advancements in UCAs. The active targeting not only makes the precise imaging possible, but also leads to targeted delivery of active components to specific local treatment sites...
October 14, 2016: Ultrasound in Medicine & Biology
Yasunori Minami, Tomohiro Minami, Hirokazu Chishina, Masashi Kono, Tadaaki Arizumi, Masahiro Takita, Norihisa Yada, Satoru Hagiwara, Hiroshi Ida, Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
OBJECTIVE: Radiofrequency ablation (RFA) induces gas bubbles in ablation zones, and the ablative margin cannot be evaluated accurately on ultrasound (US) during and immediately after RFA. This study assessed the usefulness of US-US fusion imaging to visualize the ablative margin of RFA for liver metastasis. METHODS: RFA guided by US-US fusion imaging was performed on 12 targeted tumors in 10 patients. Secondary hepatic malignancies included patients with colorectal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor (n = 1), pancreatic neuroendocrine tumor (n = 1), and adrenocortical carcinoma (n = 1)...
2016: Digestive Diseases
James J Farrell, Jennifer Moughan, Jonathan L Wong, William F Regine, Paul Schaefer, Al B Benson, John S Macdonald, Xiyong Liu, Yun Yen, Raymond Lai, Zhong Zheng, Gerold Bepler, Chandan Guha, Hany Elsaleh
OBJECTIVES: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. METHODS: Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine...
November 2016: Pancreas
Marie-France Penet, Jiefu Jin, Zhihang Chen, Zaver M Bhujwalla
With its exquisite anatomical resolution and wide-ranging functional imaging capabilities, magnetic resonance imaging (MRI) has found multiple applications in detection, staging, and monitoring treatment response in cancer. The metabolic information provided by magnetic resonance spectroscopy (MRS) is being actively investigated to complement MRI parameters, as well as existing biomarkers, in cancer detection and in monitoring response to treatment. Located at the interface of detection and therapy, theranostic imaging is a rapidly expanding new field that is showing significant promise for precision medicine of cancer...
October 2016: Topics in Magnetic Resonance Imaging: TMRI
Sankar N Maity, Mark A Titus, Revekka Gyftaki, Guanglin Wu, Jing-Fang Lu, S Ramachandran, Elsa M Li-Ning-Tapia, Christopher J Logothetis, John C Araujo, Eleni Efstathiou
Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a validated treatment target for the treatment of metastatic castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) inhibits both 17α-hydroxylase (hydroxylase) and 17,20-lyase (lyase) reactions catalyzed by CYP17A1 and thus depletes androgen biosynthesis. However, coadministration of prednisone is required to suppress the mineralocorticoid excess and cortisol depletion that result from hydroxylase inhibition. VT-464, a nonsteroidal small molecule, selectively inhibits CYP17A1 lyase and therefore does not require prednisone supplementation...
October 17, 2016: Scientific Reports
Claudia Crocini, Cecilia Ferrantini, Raffaele Coppini, Marina Scardigli, Ping Yan, Leslie M Loew, Godfrey Smith, Elisabetta Cerbai, Corrado Poggesi, Francesco S Pavone, Leonardo Sacconi
Current rescue therapies for life-threatening arrhythmias ignore the pathological electro-anatomical substrate and base their efficacy on a generalized electrical discharge. Here, we developed an all-optical platform to examine less invasive defibrillation strategies. An ultrafast wide-field macroscope was developed to optically map action potential propagation with a red-shifted voltage sensitive dye in whole mouse hearts. The macroscope was implemented with a random-access scanning head capable of drawing arbitrarily-chosen stimulation patterns with sub-millisecond temporal resolution allowing precise epicardial activation of Channelrhodopsin2 (ChR2)...
October 17, 2016: Scientific Reports
Bing-Ying Xie, Ai-Wen Wu
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy. METHODS: We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs)...
2016: Chinese Medical Journal
Apurva Jain, Milind Javle
Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology...
October 2016: Journal of Gastrointestinal Oncology
Justin Sapiezynski, Oleh Taratula, Lorna Rodriguez-Rodriguez, Tamara Minko
The review is aimed at describing modern approaches to detection as well as precision and personalized treatment of ovarian cancer. Modern methods and future directions of nanotechnology-based targeted and personalized therapy are discussed.
October 13, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xiaojing Liu, Iris L Romero, Lacey M Litchfield, Ernst Lengyel, Jason W Locasale
Repurposing metformin for cancer therapy is attractive due to its safety profile, epidemiological evidence, and encouraging data from human clinical trials. Although it is known to systemically affect glucose metabolism in liver, muscle, gut, and other tissues, the molecular determinants that predict a patient response in cancer remain unknown. Here, we carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Metformin accumulated in patient biopsies, and pathways involving nucleotide metabolism, redox, and energy status, all related to mitochondrial metabolism, were affected in treated tumors...
October 12, 2016: Cell Metabolism
Rebecca B Goody, Helen MacKay, Bethany Pitcher, Amit Oza, Lillian L Siu, John Kim, Rebecca K S Wong, Eric Chen, Carol Swallow, Jennifer Knox, Zahra Kassam, Bernard Cummings, Ron Feld, David Hedley, Geoffrey Liu, Monika K Krzyzanowska, Robert Dinniwell, Anthony M Brade, Laura A Dawson, Melania Pintilie, Jolie Ringash
PURPOSE: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. METHODS AND MATERIALS: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma...
August 31, 2016: International Journal of Radiation Oncology, Biology, Physics
Yu Kobayashi, Jun Tohyama, Tomoyuki Akiyama, Shinichi Magara, Hideshi Kawashima, Noriyuki Akasaka, Mitsuko Nakashima, Hirotomo Saitsu, Naomichi Matsumoto
Cerebral folate deficiency due to folate receptor 1 gene (FOLR1) mutations is an autosomal recessive disorder resulting from a brain-specific folate transport defect. It is characterized by late infantile onset, severe psychomotor regression, epilepsy, and leukodystrophy. We describe a consanguineous girl exhibiting severe developmental regression, intractable epilepsy, polyneuropathy, and profound hypomyelination with cortical involvement. Magnetic resonance imaging showed cortical disturbances in addition to profound hypomyelination and cerebellar atrophy...
October 12, 2016: Brain & Development
G André Ng
Antiarrhythmic drug therapy has seen significant challenges over the past 3 decades with unexpected results from clinical trials such as CAST, SWORD and more recently PALLAS showing harm in patients whom antiarrhythmic drugs were given based on their intended antiarrhythmic actions and previously demonstrated efficacy. These results question whether the precise mechanism of action of the drugs was understood and highlight the complexity of the situation where there is the combination of multiple actions of the antiarrhythmic drugs on various molecular systems, some of which may be unknown with associated adverse outcome, and their interaction with pre-existing abnormality in disease states in patients treated...
October 12, 2016: Pharmacology & Therapeutics
Gabriel L Galea, Lance E Lanyon, Joanna S Price
Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss...
October 11, 2016: Bone
Mark A D'Agostino
The standard treatment for patients with obstructive sleep apnea syndrome is positive airway pressure (PAP) therapy. However when PAP therapy fails, surgery maybe an option to alleviate the obstruction. The base of tongue plays an important role in this obstruction, and addressing the tongue base surgically can be a challenge for the head and neck surgeon. Transoral robotic surgery (TORS) using the da Vinci Surgical System provides a safe and effective way to approach and manage the base of tongue and supraglottis...
October 11, 2016: Otolaryngologic Clinics of North America
E Sala, E Mema, Y Himoto, H Veeraraghavan, J D Brenton, A Snyder, B Weigelt, H A Vargas
Tumour heterogeneity in cancers has been observed at the histological and genetic levels, and increased levels of intra-tumour genetic heterogeneity have been reported to be associated with adverse clinical outcomes. This review provides an overview of radiomics, radiogenomics, and habitat imaging, and examines the use of these newly emergent fields in assessing tumour heterogeneity and its implications. It reviews the potential value of radiomics and radiogenomics in assisting in the diagnosis of cancer disease and determining cancer aggressiveness...
October 11, 2016: Clinical Radiology
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