Releasing the Constraints on Aphasia Therapy: The Positive Impact of Gesture and Multimodality Treatments

ERIC Educational Resources Information Center

Rose, Miranda L.

2013-01-01

Purpose: There is a 40-year history of interest in the use of arm and hand gestures in treatments that target the reduction of aphasic linguistic impairment and compensatory methods of communication (Rose, 2006). Arguments for constraining aphasia treatment to the verbal modality have arisen from proponents of constraint-induced aphasia therapy…

What is the role of imaging in the clinical diagnosis of osteoarthritis and disease management?

PubMed

Wang, Xia; Oo, Win Min; Linklater, James M

2018-05-01

While OA is predominantly diagnosed on the basis of clinical criteria, imaging may aid with differential diagnosis in clinically suspected cases. While plain radiographs are traditionally the first choice of imaging modality, MRI and US also have a valuable role in assessing multiple pathologic features of OA, although each has particular advantages and disadvantages. Although modern imaging modalities provide the capability to detect a wide range of osseous and soft tissue (cartilage, menisci, ligaments, synovitis, effusion) OA-related structural damage, this extra information has not yet favourably influenced the clinical decision-making and management process. Imaging is recommended if there are unexpected rapid changes in clinical outcomes to determine whether it relates to disease severity or an additional diagnosis. On developing specific treatments, imaging serves as a sensitive tool to measure treatment response. This narrative review aims to describe the role of imaging modalities to aid in OA diagnosis, disease progression and management. It also provides insight into the use of these modalities in finding targeted treatment strategies in clinical research.

Characterizing smoking, cessation services, and quit interest across outpatient substance abuse treatment modalities

PubMed Central

McClure, Erin A.; Acquavita, Shauna P.; Dunn, Kelly E.; Stoller, Kenneth B.; Stitzer, Maxine L.

2013-01-01

The majority of individuals seeking treatment for substance use disorders are cigarette smokers, yet smoking cessation is rarely addressed during treatment. Conducting a detailed smoking-related characterization of substance abuse treatment patients across treatment modalities may facilitate the development of tailored treatment strategies. This study administered a battery of self-report instruments to compare tobacco use, quit attempts, smoking knowledge and attitudes, program services, and interest in quitting among smoking patients enrolled in opioid replacement therapy (ORT) vs. non-opioid replacement (non-ORT). ORT compared with non-ORT participants smoked more heavily, had greater tobacco dependence, and endorsed greater exposure to smoking cessation services at their treatment programs. Favorable attitudes towards cessation during treatment were found within both groups. These data identify several potential clinical targets, most notably including confidence in abstaining and attitudes toward cessation pharmacotherapies that may be addressed by substance abuse treatment clinics. PMID:23988192

IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

DTIC Science & Technology

2013-02-01

therapies (surgery, radiation and chemotherapy) have reached a therapeutic ceiling in improving the five- year overall survival rate of non-small cell...poor understanding of the disease and its resistance to the therapy . Lung cancer is a heterogeneous disease, resulting from accumulated genetic... a new promising approach to treatment of lung cancer. The program project IMPACT has proposed to integrate targeted therapy in the lung cancer

Methodologies in the modeling of combined chemo-radiation treatments

NASA Astrophysics Data System (ADS)

Grassberger, C.; Paganetti, H.

2016-11-01

The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling. While treatment optimization and outcome modeling does focus mainly on the effects of radiation, treatment modalities such as chemotherapy are treated independently or are even neglected entirely. This review summarizes the published efforts to model combined modality treatments combining radiation and chemotherapy. These models will play an increasing role in optimizing cancer therapy not only from a radiation and drug dosage standpoint, but also in terms of spatial and temporal optimization of treatment schedules.

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector-p53.

PubMed

Baliaka, A; Zarogoulidis, P; Domvri, K; Hohenforst-Schmidt, W; Sakkas, A; Huang, H; Le Pivert, P; Koliakos, G; Koliakou, E; Kouzi-Koliakos, K; Tsakiridis, K; Chioti, A; Siotou, E; Cheva, A; Zarogoulidis, K; Sakkas, L

2014-02-01

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

"Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy.

PubMed

Kemp, Jessica A; Shim, Min Suk; Heo, Chan Yeong; Kwon, Young Jik

2016-03-01

The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

Chained lightning: part III--Emerging technology, novel therapeutic strategies, and new energy modalities for radiosurgery.

PubMed

Hoh, Daniel J; Liu, Charles Y; Chen, Joseph C T; Pagnini, Paul G; Yu, Cheng; Wang, Michael Y; Apuzzo, Michael L J

2007-12-01

Radiosurgery is fundamentally the harnessing of energy and delivering it to a focal target for a therapeutic effect. The evolution of radiosurgical technology and practice has served toward refining methodologies for better conformal energy delivery. In the past, this has resulted in developing strategies for improved beam generation and delivery. Ultimately, however, our current instrumentation and treatment modalities may be approaching a practical limit with regard to further optimizing energy containment. In looking forward, several strategies are emerging to circumvent these limitations and improve conformal radiosurgery. Refinement of imaging techniques through functional imaging and nanoprobes for cancer detection may benefit lesion localization and targeting. Methods for enhancing the biological effect while reducing radiation-induced changes are being examined through dose fractionation schedules. Radiosensitizers and photosensitizers are being investigated as agents for modulating the biological response of tissues to radiation and alternative energy forms. Discovery of new energy modalities is being pursued through development of microplanar beams, free electron lasers, and high-intensity focused ultrasound. The exploration of these future possibilities will provide the tools for radiosurgical treatment of a broader spectrum of diseases for the next generation.

Working Memory and Neurofeedback.

PubMed

YuLeung To, Eric; Abbott, Kathy; Foster, Dale S; Helmer, D'Arcy

2016-01-01

Impairments in working memory are typically associated with impairments in other cognitive faculties such as attentional processes and short-term memory. This paper briefly introduces neurofeedback as a treatment modality in general, and, more specifically, we review several of the current modalities successfully used in neurofeedback (NF) for the treatment of working memory deficits. Two case studies are presented to illustrate how neurofeedback is applied in treatment. The development of Low Resolution Electromagnetic Tomography (LORETA) and its application in neurofeedback now makes it possible to specifically target deep cortical/subcortical brain structures. Developments in neuroscience concerning neural networks, combined with highly specific yet practical NF technologies, makes neurofeedback of particular interest to neuropsychological practice, including the emergence of specific methodologies for treating very difficult working memory (WM) problems.

Prevention of age-related macular degeneration.

PubMed

Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

2011-02-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruan, D; Shao, W; Low, D

Purpose: To evaluate and test the hypothesis that plan quality may be systematically affected by treatment delivery techniques and target-tocritical structure geometric relationship in radiotherapy for brain tumor. Methods: Thirty-four consecutive brain tumor patients treated between 2011–2014 were analyzed. Among this cohort, 10 were planned with 3DCRT, 11 with RadipArc, and 13 with helical IMRT on TomoTherapy. The selected dosimetric endpoints (i.e., PTV V100, maximum brainstem/chiasm/ optic nerve doses) were considered as a vector in a highdimensional space. A Pareto analysis was performed to identify the subset of Pareto-efficient plans.The geometric relationships, specifically the overlapping volume and centroid-of-mass distance betweenmore » each critical structure to the PTV were extracted as potential geometric features. The classification-tree analyses were repeated using these geometric features with and without the treatment modality as an additional categorical predictor. In both scenarios, the dominant features to prognosticate the Pareto membership were identified and the tree structures to provide optimal inference were recorded. The classification performance was further analyzed to determine the role of treatment modality in affecting plan quality. Results: Seven Pareto-efficient plans were identified based on dosimetric endpoints (3 from 3DCRT, 3 from RapicArc, 1 from Tomo), which implies that the evaluated treatment modality may have a minor influence on plan quality. Classification trees with/without the treatment modality as a predictor both achieved accuracy of 88.2%: with 100% sensitivity and 87.1% specificity for the former, and 66.7% sensitivity and 96.0% specificity for the latter. The coincidence of accuracy from both analyses further indicates no-to-weak dependence of plan quality on treatment modality. Both analyses have identified the brainstem to PTV distance as the primary predictive feature for Pareto-efficiency. Conclusion: Pareto evaluation and classification-tree analyses have indicated that plan quality depends strongly on geometry for brain tumor, specifically PTV-tobrain-stem-distance but minimally on treatment modality.« less

Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor- Associated...3. DATES COVERED 31 Aug 2015 - 30 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting MEK5 Enhances Radiosensitivity of Human Prostate...therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to

Cross-modal links among vision, audition, and touch in complex environments.

PubMed

Ferris, Thomas K; Sarter, Nadine B

2008-02-01

This study sought to determine whether performance effects of cross-modal spatial links that were observed in earlier laboratory studies scale to more complex environments and need to be considered in multimodal interface design. It also revisits the unresolved issue of cross-modal cuing asymmetries. Previous laboratory studies employing simple cues, tasks, and/or targets have demonstrated that the efficiency of processing visual, auditory, and tactile stimuli is affected by the modality, lateralization, and timing of surrounding cues. Very few studies have investigated these cross-modal constraints in the context of more complex environments to determine whether they scale and how complexity affects the nature of cross-modal cuing asymmetries. Amicroworld simulation of battlefield operations with a complex task set and meaningful visual, auditory, and tactile stimuli was used to investigate cuing effects for all cross-modal pairings. Significant asymmetric performance effects of cross-modal spatial links were observed. Auditory cues shortened response latencies for collocated visual targets but visual cues did not do the same for collocated auditory targets. Responses to contralateral (rather than ipsilateral) targets were faster for tactually cued auditory targets and each visual-tactile cue-target combination, suggesting an inhibition-of-return effect. The spatial relationships between multimodal cues and targets significantly affect target response times in complex environments. The performance effects of cross-modal links and the observed cross-modal cuing asymmetries need to be examined in more detail and considered in future interface design. The findings from this study have implications for the design of multimodal and adaptive interfaces and for supporting attention management in complex, data-rich domains.

Missing Modality Transfer Learning via Latent Low-Rank Constraint.

PubMed

Ding, Zhengming; Shao, Ming; Fu, Yun

2015-11-01

Transfer learning is usually exploited to leverage previously well-learned source domain for evaluating the unknown target domain; however, it may fail if no target data are available in the training stage. This problem arises when the data are multi-modal. For example, the target domain is in one modality, while the source domain is in another. To overcome this, we first borrow an auxiliary database with complete modalities, then consider knowledge transfer across databases and across modalities within databases simultaneously in a unified framework. The contributions are threefold: 1) a latent factor is introduced to uncover the underlying structure of the missing modality from the known data; 2) transfer learning in two directions allows the data alignment between both modalities and databases, giving rise to a very promising recovery; and 3) an efficient solution with theoretical guarantees to the proposed latent low-rank transfer learning algorithm. Comprehensive experiments on multi-modal knowledge transfer with missing target modality verify that our method can successfully inherit knowledge from both auxiliary database and source modality, and therefore significantly improve the recognition performance even when test modality is inaccessible in the training stage.

Functional Imaging for Prostate Cancer: Therapeutic Implications

PubMed Central

Aparici, Carina Mari; Seo, Youngho

2012-01-01

Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

MO-FG-BRD-01: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: Introduction and KV Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fahimian, B.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

MO-FG-BRD-04: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: MR Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Low, D.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

MO-FG-BRD-02: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: MV Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berbeco, R.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

MO-FG-BRD-03: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: EM Tracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keall, P.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

MO-FG-BRD-00: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

Optical Quality, Threshold Target Identification and Military Target Task Performance After Advanced Keratorefractive Surgery

DTIC Science & Technology

2010-05-01

PRK vs . LASIK ) will no longer randomized but rather the patient a...commercial workstation & software. Analysis will determine the effect on visual performance of the different treatments (WFO PRK vs . WFO LASIK vs . WFG PRK ...Overall objective. To determine the effect of two types of wavefront modalities (WFG vs . WFO) and two types of refractive surgery ( PRK vs . LASIK )

SU-E-J-109: Accurate Contour Transfer Between Different Image Modalities Using a Hybrid Deformable Image Registration and Fuzzy Connected Image Segmentation Method.

PubMed

Yang, C; Paulson, E; Li, X

2012-06-01

To develop and evaluate a tool that can improve the accuracy of contour transfer between different image modalities under challenging conditions of low image contrast and large image deformation, comparing to a few commonly used methods, for radiation treatment planning. The software tool includes the following steps and functionalities: (1) accepting input of images of different modalities, (2) converting existing contours on reference images (e.g., MRI) into delineated volumes and adjusting the intensity within the volumes to match target images (e.g., CT) intensity distribution for enhanced similarity metric, (3) registering reference and target images using appropriate deformable registration algorithms (e.g., B-spline, demons) and generate deformed contours, (4) mapping the deformed volumes on target images, calculating mean, variance, and center of mass as the initialization parameters for consecutive fuzzy connectedness (FC) image segmentation on target images, (5) generate affinity map from FC segmentation, (6) achieving final contours by modifying the deformed contours using the affinity map with a gradient distance weighting algorithm. The tool was tested with the CT and MR images of four pancreatic cancer patients acquired at the same respiration phase to minimize motion distortion. Dice's Coefficient was calculated against direct delineation on target image. Contours generated by various methods, including rigid transfer, auto-segmentation, deformable only transfer and proposed method, were compared. Fuzzy connected image segmentation needs careful parameter initialization and user involvement. Automatic contour transfer by multi-modality deformable registration leads up to 10% of accuracy improvement over the rigid transfer. Two extra proposed steps of adjusting intensity distribution and modifying the deformed contour with affinity map improve the transfer accuracy further to 14% averagely. Deformable image registration aided by contrast adjustment and fuzzy connectedness segmentation improves the contour transfer accuracy between multi-modality images, particularly with large deformation and low image contrast. © 2012 American Association of Physicists in Medicine.

Nonmetastatic Castration-resistant Prostate Cancer: A Modern Perspective.

PubMed

Cancian, Madeline; Renzulli, Joseph F

2018-06-01

Nonmetastatic castration-resistant prostate cancer (nmCRPC) presents a challenge to urologists as currently there are no Food and Drug Administration-approved therapies. However, there are new imaging modalities, including fluciclovine positron emission tomography-computed tomography and Ga-PSMA (prostate specific membrane antigent) positron emission tomography-computed tomography, which are improving accuracy of diagnosis. With improved imaging, we are better able to target therapy. Today there are 3 ongoing clinical trials studying second-generation antiandrogens in nmCRPC, which hold the promise of a new treatment paradigm. In this article, we will review the new imaging techniques and the rationale behind novel treatment modalities in nmCRPC. Copyright © 2018 Elsevier Inc. All rights reserved.

Prevention of age-related macular degeneration

PubMed Central

Koo, Simon Chi Yan; Chan, Clement Wai Nang

2010-01-01

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

Combating atherosclerosis with targeted nanomedicines: recent advances and future prospective

PubMed Central

Nakhlband, Ailar; Eskandani, Morteza; Saeedi, Nazli; Ghaffari, Samad; Garjani, Alireza

2018-01-01

Introduction: Cardiovascular diseases (CVDs) is recognized as the leading cause of mortality worldwide. The increasing prevalence of such disease demands novel therapeutic and diagnostic approaches to overcome associated clinical/social issues. Recent advances in nanotechnology and biological sciences have provided intriguing insights to employ targeted Nanomachines to the desired location as imaging, diagnosis, and therapeutic modalities. Nanomedicines as novel tools for enhanced drug delivery, imaging, and diagnosis strategies have shown great promise to combat cardiovascular diseases. Methods: In the current study, we intend to review the most recent studies on the nano-based strategies for improved management of CVDs. Results: A cascade of events results in the formation of atheromatous plaque and arterial stenosis. Furthermore, recent studies have shown that nanomedicines have displayed unique functionalities and provided de novo applications in the diagnosis and treatment of atherosclerosis. Conclusion: Despite some limitations, nanomedicines hold considerable potential in the prevention, diagnosis, and treatment of various ailments including atherosclerosis. Fewer side effects, amenable physicochemical properties and multi-potential application of such nano-systems are recognized through various investigations. Therefore, it is strongly believed that with targeted drug delivery to atherosclerotic lesions and plaque, management of onset and progression of disease would be more efficient than classical treatment modalities. PMID:29713603

Current treatment options for recurrent/metastatic head and neck cancer: a post-ASCO 2011 update and review of last year's literature.

PubMed

Kurzweg, T; Möckelmann, N; Laban, S; Knecht, R

2012-10-01

The majority of patients with a squamous cell carcinoma of the head and neck present with locally advanced tumors. The first-line treatment of locally advanced tumor stages consists of a combined modality management. Despite these aggressive protocols, many patients develop locoregional recurrences or metastasis and place particularly high demands on the interdisciplinary treatment team. Treatment with a curative intent must be differentiated from a palliative one. In addition to prior treatment, resectability, age and performance status, patient wishes must be taken into consideration in treatment planning, especially considering that most therapies offer little to no overall survival benefit. Salvage surgery, chemo- and target therapies, and reirradiation are head and neck surgeon's and radiooncologist's weapons in the fight against these strong opponents. This review focuses on publications and meeting news from last year and reviews the current status of the clinical application of each treatment modality in recurrent or metastatic head and neck cancer.

Basic immunology of antibody targeted radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Jeffrey Y.C.

2006-10-01

Antibody targeted radiotherapy brings an important new treatment modality to Radiation oncology clinic. Radiation dose to tumor and normal tissues are determined by a complex interplay of antibody, antigen, tumor, radionuclide, and host-related factors. A basic understanding of these immunologic and physiologic factors is important to optimally utilize this therapy in the clinic. Preclinical and clinical studies need to be continued to broaden our understanding and to develop new strategies to further improve the efficacy of this promising form of targeted therapy.

Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases.

PubMed

Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata; Rudnicka, Lidia

2016-08-01

Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment - a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab).

Dissociable identity- and modality-specific neural representations as revealed by cross-modal nonspatial inhibition of return.

PubMed

Chi, Yukai; Yue, Zhenzhu; Liu, Yupin; Mo, Lei; Chen, Qi

2014-08-01

There are ongoing debates on whether object concepts are coded as supramodal identity-based or modality-specific representations in the human brain. In this fMRI study, we adopted a cross-modal "prime-neutral cue-target" semantic priming paradigm, in which the prime-target relationship was manipulated along both the identity and the modality dimensions. The prime and the target could refer to either the same or different semantic identities, and could be delivered via either the same or different sensory modalities. By calculating the main effects and interactions of this 2 (identity cue validity: "Identity_Cued" vs. "Identity_Uncued") × 2 (modality cue validity: "Modality_Cued" vs. "Modality_Uncued") factorial design, we aimed at dissociating three neural networks involved in creating novel identity-specific representations independent of sensory modality, in creating modality-specific representations independent of semantic identity, and in evaluating changes of an object along both the identity and the modality dimensions, respectively. Our results suggested that bilateral lateral occipital cortex was involved in creating a new supramodal semantic representation irrespective of the input modality, left dorsal premotor cortex, and left intraparietal sulcus were involved in creating a new modality-specific representation irrespective of its semantic identity, and bilateral superior temporal sulcus was involved in creating a representation when the identity and modality properties were both cued or both uncued. In addition, right inferior frontal gyrus showed enhanced neural activity only when both the identity and the modality of the target were new, indicating its functional role in novelty detection. Copyright © 2014 Wiley Periodicals, Inc.

NTCP reduction for advanced head and neck cancer patients using proton therapy for complete or sequential boost treatment versus photon therapy.

PubMed

Jakobi, Annika; Stützer, Kristin; Bandurska-Luque, Anna; Löck, Steffen; Haase, Robert; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniel; Perez, Damien; Lühr, Armin; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Perrin, Rosalind; Richter, Christian

2015-01-01

To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only. For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (∆NTCPIMXT-IMPT) as well as between IMXT and the mixed modality treatment (∆NTCPIMXT-Mix) were calculated. Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, ∆NTCPIMXT-Mix values were a factor 2-10 smaller than ∆NTCPIMXT-IMPT. Assuming a threshold of ≥ 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, ∆NTCP ≥ 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost. The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering the toxicities xerostomia and dysphagia, if a feasible strategy for patient anatomy changes is implemented.

Microwave pumped high-efficient thermoacoustic tumor therapy with single wall carbon nanotubes.

PubMed

Wen, Liewei; Ding, Wenzheng; Yang, Sihua; Xing, Da

2016-01-01

The ultra-short pulse microwave could excite to the strong thermoacoustic (TA) shock wave and deeply penetrate in the biological tissues. Based on this, we developed a novel deep-seated tumor therapy modality with mitochondria-targeting single wall carbon nanotubes (SWNTs) as microwave absorbing agents, which act efficiently to convert ultra-short microwave energy into TA shock wave and selectively destroy the targeted mitochondria, thereby inducing apoptosis in cancer cells. After the treatment of SWNTs (40 μg/mL) and ultra-short microwave (40 Hz, 1 min), 77.5% of cancer cells were killed and the vast majority were caused by apoptosis that initiates from mitochondrial damage. The orthotopic liver cancer mice were established as deep-seated tumor model to investigate the anti-tumor effect of mitochondria-targeting TA therapy. The results suggested that TA therapy could effectively inhibit the tumor growth without any observable side effects, while it was difficult to achieve with photothermal or photoacoustic therapy. These discoveries implied the potential application of TA therapy in deep-seated tumor models and should be further tested for development into a promising therapeutic modality for cancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treat-to-target trials in diabetes.

PubMed

Wangnoo, Subhash K; Sethi, Bipin; Sahay, Rakesh K; John, Mathew; Ghosal, Samit; Sharma, Surendra K

2014-03-01

Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols.

Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system

NASA Astrophysics Data System (ADS)

Lehmann, Joerg; Hartmann Siantar, Christine; Wessol, Daniel E.; Wemple, Charles A.; Nigg, David; Cogliati, Josh; Daly, Tom; Descalle, Marie-Anne; Flickinger, Terry; Pletcher, David; DeNardo, Gerald

2005-03-01

The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4—2%, MCNP—10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of the drug pharmacokinetics in MTR can only be properly accounted for by image-based, patient-specific treatment planning, as has been common in external beam radiation therapy for many years. MINERVA offers 3D Monte Carlo-based MTR treatment planning as its first integrated operational capability. The new MINERVA system will ultimately incorporate capabilities for a comprehensive list of radiation therapies. In progress are modules for external beam photon-electron therapy and boron neutron capture therapy (BNCT). Brachytherapy and proton therapy are planned. Through the open application programming interface (API), other groups can add their own modules and share them with the community.

Molecular Imaging: Current Status and Emerging Strategies

PubMed Central

Pysz, Marybeth A.; Gambhir, Sanjiv S.; Willmann, Jürgen K.

2011-01-01

In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific therapeutic treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use PET- or SPECT-based techniques. In ongoing preclinical research novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multimodality molecular imaging. Contrast-enhanced molecular ultrasound with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and ultrasound imaging with molecularly-targeted microbubbles are attractive strategies since they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and ultrasound modalities involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with ultrasound. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:20541650

Development of Immunopathogenesis Strategies to Treat Behçet's Disease

PubMed Central

Köse, Osman

2012-01-01

Behçet disease is a chronic relapsing vasculitis with unclear etiology and immunopathogenesis. Antigenic stimuli, antigen presenting cells, T cells, monocyte, and neutrophil and endothelial cells are major parts of the pathology of the disease. Understanding of the new pathogenic mechanisms based on molecular structure of the disease helps us in improving the novel therapeutic modalities. These drugs target specific and nonspecific inhibition of the immun system. These therapies include biologic agents, new topical and systemic immunosuppressants, tolerizing agents, and immunoablation. Novel treatment will be promising to treat the especially recalcitrant cases to conventional therapy. In this paper, new aspect of the immunopathogenesis of Behçet's diseases and novel treatment modalities will be discussed. PMID:22550612

Verruca plana as a complication of CO2 laser treatment: a case report.

PubMed

Winn, Aubrey E; Kentosh, Joshua; Bingham, Jonathan L

2015-04-01

Carbon dioxide (CO2) laser treatment is a common therapeutic modality for many dermatologic conditions. It uses a high energy, infrared beam of light, which selectively targets water-containing tissue resulting in controlled ablative resurfacing. This modality, however, can manifest significant cosmetic side effects. Here we report a case of verruca plana manifesting as a response to CO2 laser treatment. A 74-year-old female with recent Mohs surgery for a basal cell carcinoma, presented for full-face-fractionated CO2 treatment to address her surgical scars in addition to treating her mild diffuse actinic damage. Six weeks post treatment, the patient developed erythematous thin plaques over the areas that had been treated. Histology was consistent with verruca plana. Lesions showed mild improvement with topical tretinoin. Verruca plana are benign and typically self-limited; however, they can present a significant cosmetic burden to patients and are an important complication to consider when performing elective cosmetic procedures.

On-line MR imaging for dose validation of abdominal radiotherapy

NASA Astrophysics Data System (ADS)

Glitzner, M.; Crijns, S. P. M.; de Senneville, B. Denis; Kontaxis, C.; Prins, F. M.; Lagendijk, J. J. W.; Raaymakers, B. W.

2015-11-01

For quality assurance and adaptive radiotherapy, validation of the actual delivered dose is crucial. Intrafractional anatomy changes cannot be captured satisfactorily during treatment with hitherto available imaging modalitites. Consequently, dose calculations are based on the assumption of static anatomy throughout the treatment. However, intra- and interfraction anatomy is dynamic and changes can be significant. In this paper, we investigate the use of an MR-linac as a dose tracking modality for the validation of treatments in abdominal targets where both respiratory and long-term peristaltic and drift motion occur. The on-line MR imaging capability of the modality provides the means to perform respiratory gating of both delivery and acquisition yielding a model-free respiratory motion management under free breathing conditions. In parallel to the treatment, the volumetric patient anatomy was captured and used to calculate the applied dose. Subsequently, the individual doses were warped back to the planning grid to obtain the actual dose accumulated over the entire treatment duration. Ultimately, the planned dose was validated by comparison with the accumulated dose. Representative for a site subject to breathing modulation, two kidney cases (25 Gy target dose) demonstrated the working principle on volunteer data and simulated delivery. The proposed workflow successfully showed its ability to track local dosimetric changes. Integration of the on-line anatomy information could reveal local dose variations  -2.3-1.5 Gy in the target volume of a volunteer dataset. In the adjacent organs at risk, high local dose errors ranging from  -2.5 to 1.9 Gy could be traced back.

Role of functional imaging in the development and refinement of invasive neuromodulation for psychiatric disorders

PubMed Central

Williams, Nolan R; Taylor, Joseph J; Lamb, Kayla; Hanlon, Colleen A; Short, E Baron; George, Mark S

2014-01-01

Deep brain stimulation (DBS) is emerging as a powerful tool for the alleviation of targeted symptoms in treatment-resistant neuropsychiatric disorders. Despite the expanding use of neuropsychiatric DBS, the mechanisms responsible for its effects are only starting to be elucidated. Several modalities such as quantitative electroencephalography as well a intraoperative recordings have been utilized to attempt to understand the underpinnings of this new treatment modality, but functional imaging appears to offer several unique advantages. Functional imaging techniques like positron emission tomography, single photon emission computed tomography and functional magnetic resonance imaging have been used to examine the effects of focal DBS on activity in a distributed neural network. These investigations are critical for advancing the field of invasive neuromodulation in a safe and effective manner, particularly in terms of defining the neuroanatomical targets and refining the stimulation protocols. The purpose of this review is to summarize the current functional neuroimaging findings from neuropsychiatric DBS implantation for three disorders: treatment-resistant depression, obsessive-compulsive disorder, and Tourette syndrome. All of the major targets will be discussed (Nucleus accumbens, anterior limb of internal capsule, subcallosal cingulate, Subthalamic nucleus, Centromedial nucleus of the thalamus-Parafasicular complex, frontal pole, and dorsolateral prefrontal cortex). We will also address some apparent inconsistencies within this literature, and suggest potential future directions for this promising area. PMID:25349661

Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Specht, Lena, E-mail: lena.specht@regionh.dk; Yahalom, Joachim; Illidge, Tim

2014-07-15

Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solelymore » on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines.« less

Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG).

PubMed

Specht, Lena; Yahalom, Joachim; Illidge, Tim; Berthelsen, Anne Kiil; Constine, Louis S; Eich, Hans Theodor; Girinsky, Theodore; Hoppe, Richard T; Mauch, Peter; Mikhaeel, N George; Ng, Andrea

2014-07-15

Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines. Copyright © 2014 Elsevier Inc. All rights reserved.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy

NASA Astrophysics Data System (ADS)

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-08-01

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments. Electronic supplementary information (ESI) available: Experimental details, peptide structures, molecular weights, and additional data. See DOI: 10.1039/c5nr03862f

Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy.

PubMed

Tang, Xiang-Jun; Sun, Xu-Yong; Huang, Kuan-Ming; Zhang, Li; Yang, Zhuo-Shun; Zou, Dan-Dan; Wang, Bin; Warnock, Garth L; Dai, Long-Jun; Luo, Jie

2015-12-29

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.

How to train your T cell: genetically engineered chimeric antigen receptor T cells versus bispecific T-cell engagers to target CD19 in B acute lymphoblastic leukemia.

PubMed

Ruella, Marco; Gill, Saar

2015-06-01

Antigen-specific T cell-based immunotherapy is getting its day in the sun. The contemporaneous development of two potent CD19-specific immunotherapeutic modalities for the treatment of B-cell malignancies provides exciting opportunities for patients, physicians and scientists alike. Patients with relapsed, refractory or poor-risk B-cell acute lymphoblastic leukemia (ALL) previously had few therapeutic options and now have two potential new lifelines. Physicians will have the choice between two powerful modalities and indeed could potentially enroll some patients on trials exploring both modalities if needed. For scientists interested in tumor immunology, the advent of chimeric antigen receptor T-cell therapy and of bispecific T-cell engagers (BiTEs) provides unprecedented opportunities to explore the promise and limitations of antigen-specific T-cell therapy in the context of human leukemia. In this article, we compare chimeric antigen receptor T cells and BiTEs targeting CD19 in B-cell ALL in the setting of the available clinical literature.

[Why is brachytherapy still essential in 2017?

PubMed

Haie-Méder, C; Maroun, P; Fumagalli, I; Lazarescu, I; Dumas, I; Martinetti, F; Chargari, C

2018-05-16

These recent years, brachytherapy has benefited from imaging modalities advances. A more systematic use of tomodensitometric, ultrasonographic and MRI images during brachytherapy procedures has allowed an improvement in target and organs at risk assessment as well as their relationship with the applicators. New concepts integrating tumor regression during treatment have been defined and have been clinically validated. New applicators have been developed and are commercially available. Optimization processes have been developed, integrating hypofractionation modalities leading to tumor control improvement. All these opportunities led to further development of brachytherapy, with indisputable ballistic advantages, especially compared to external irradiation. Copyright © 2018. Published by Elsevier SAS.

Alternating between pro- and antisaccades: switch-costs manifest via decoupling the spatial relations between stimulus and response.

PubMed

Heath, Matthew; Gillen, Caitlin; Samani, Ashna

2016-03-01

Antisaccades are a nonstandard task requiring a response mirror-symmetrical to the location of a target. The completion of an antisaccade has been shown to delay the reaction time (RT) of a subsequent prosaccade, whereas the converse switch elicits a null RT cost (i.e., the unidirectional prosaccade switch-cost). The present study sought to determine whether the prosaccade switch-cost arises from low-level interference specific to the sensory features of a target (i.e., modality-dependent) or manifests via the high-level demands of dissociating the spatial relations between stimulus and response (i.e., modality-independent). Participants alternated between pro- and antisaccades wherein the target associated with the response alternated between visual and auditory modalities. Thus, the present design involved task-switch (i.e., switching from a pro- to antisaccade and vice versa) and modality-switch (i.e., switching from a visual to auditory target and vice versa) trials as well as their task- and modality-repetition counterparts. RTs were longer for modality-switch than modality-repetition trials. Notably, however, modality-switch trials did not nullify or lessen the unidirectional prosaccade switch-cost; that is, the magnitude of the RT cost for task-switch prosaccades was equivalent across modality-switch and modality-repetition trials. Thus, competitive interference within a sensory modality does not contribute to the unidirectional prosaccade switch-cost. Instead, the modality-independent findings evince that dissociating the spatial relations between stimulus and response instantiates a high-level and inertially persistent nonstandard task-set that impedes the planning of a subsequent prosaccade.

IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

DTIC Science & Technology

2014-02-01

DRP-1: Treatment of Malignant Pleural Effusion with ZD6474, a Novel VEGFR and EGFR TK Inhibitor (PI and co-PI: Roy Herbst, M.D., Ph.D., Carlos...Jimenez, M.D.) Recurrent malignant pleural effusion is a debilitating clinical problem that requires palliation with repeated therapeutic...thoracentesis or pleurodesis (Putnam, J Surg Clin North Am 2002). Malignant pleural effusions have been associated with high levels of VEGF. Treatment with a

Results From the Imaging and Radiation Oncology Core Houston's Anthropomorphic Phantoms Used for Proton Therapy Clinical Trial Credentialing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, Paige A., E-mail: pataylor@mdanderson.org; Kry, Stephen F.; Alvarez, Paola

Purpose: The purpose of this study was to summarize the findings of anthropomorphic proton phantom irradiations analyzed by the Imaging and Radiation Oncology Core Houston QA Center (IROC Houston). Methods and Materials: A total of 103 phantoms were irradiated by proton therapy centers participating in clinical trials. The anthropomorphic phantoms simulated heterogeneous anatomy of a head, liver, lung, prostate, and spine. Treatment plans included those for scattered, uniform scanning, and pencil beam scanning beam delivery modalities using 5 different treatment planning systems. For every phantom irradiation, point doses and planar doses were measured using thermoluminescent dosimeters (TLD) and film, respectively. Differencesmore » between measured and planned doses were studied as a function of phantom, beam delivery modality, motion, repeat attempt, treatment planning system, and date of irradiation. Results: The phantom pass rate (overall, 79%) was high for simple phantoms and lower for phantoms that introduced higher levels of difficulty, such as motion, multiple targets, or increased heterogeneity. All treatment planning systems overestimated dose to the target, compared to TLD measurements. Errors in range calculation resulted in several failed phantoms. There was no correlation between treatment planning system and pass rate. The pass rates for each individual phantom are not improving over time, but when individual institutions received feedback about failed phantom irradiations, pass rates did improve. Conclusions: The proton phantom pass rates are not as high as desired and emphasize potential deficiencies in proton therapy planning and/or delivery. There are many areas for improvement with the proton phantom irradiations, such as treatment planning system dose agreement, range calculations, accounting for motion, and irradiation of multiple targets.« less

Cross-modal versus within-modal recall: differences in behavioral and brain responses.

PubMed

Butler, Andrew J; James, Karin H

2011-10-31

Although human experience is multisensory in nature, previous research has focused predominantly on memory for unisensory as opposed to multisensory information. In this work, we sought to investigate behavioral and neural differences between the cued recall of cross-modal audiovisual associations versus within-modal visual or auditory associations. Participants were presented with cue-target associations comprised of pairs of nonsense objects, pairs of nonsense sounds, objects paired with sounds, and sounds paired with objects. Subsequently, they were required to recall the modality of the target given the cue while behavioral accuracy, reaction time, and blood oxygenation level dependent (BOLD) activation were measured. Successful within-modal recall was associated with modality-specific reactivation in primary perceptual regions, and was more accurate than cross-modal retrieval. When auditory targets were correctly or incorrectly recalled using a cross-modal visual cue, there was re-activation in auditory association cortex, and recall of information from cross-modal associations activated the hippocampus to a greater degree than within-modal associations. Findings support theories that propose an overlap between regions active during perception and memory, and show that behavioral and neural differences exist between within- and cross-modal associations. Overall the current study highlights the importance of the role of multisensory information in memory. Copyright © 2011 Elsevier B.V. All rights reserved.

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollom, Erqi L.; Deng, Lei; Pai, Reetesh K.

2015-07-01

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action ofmore » toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.« less

Multimodality Tumor Delineation and Predictive Modelling via Fuzzy-Fusion Deformable Models and Biological Potential Functions

NASA Astrophysics Data System (ADS)

Wasserman, Richard Marc

The radiation therapy treatment planning (RTTP) process may be subdivided into three planning stages: gross tumor delineation, clinical target delineation, and modality dependent target definition. The research presented will focus on the first two planning tasks. A gross tumor target delineation methodology is proposed which focuses on the integration of MRI, CT, and PET imaging data towards the generation of a mathematically optimal tumor boundary. The solution to this problem is formulated within a framework integrating concepts from the fields of deformable modelling, region growing, fuzzy logic, and data fusion. The resulting fuzzy fusion algorithm can integrate both edge and region information from multiple medical modalities to delineate optimal regions of pathological tissue content. The subclinical boundaries of an infiltrating neoplasm cannot be determined explicitly via traditional imaging methods and are often defined to extend a fixed distance from the gross tumor boundary. In order to improve the clinical target definition process an estimation technique is proposed via which tumor growth may be modelled and subclinical growth predicted. An in vivo, macroscopic primary brain tumor growth model is presented, which may be fit to each patient undergoing treatment, allowing for the prediction of future growth and consequently the ability to estimate subclinical local invasion. Additionally, the patient specific in vivo tumor model will be of significant utility in multiple diagnostic clinical applications.

Molecular targeted therapy for the treatment of gastric cancer.

PubMed

Xu, Wenting; Yang, Zhen; Lu, Nonghua

2016-01-04

Despite the global decline in the incidence and mortality of gastric cancer, it remains one of the most common malignant tumors of the digestive system. Although surgical resection is the preferred treatment for gastric cancer, chemotherapy is the preferred treatment for recurrent and advanced gastric cancer patients who are not candidates for reoperation. The short overall survival and lack of a standard chemotherapy regimen make it important to identify novel treatment modalities for gastric cancer. Within the field of tumor biology, molecular targeted therapy has attracted substantial attention to improve the specificity of anti-cancer efficacy and significantly reduce non-selective resistance and toxicity. Multiple clinical studies have confirmed that molecular targeted therapy acts on various mechanisms of gastric cancer, such as the regulation of epidermal growth factor, angiogenesis, immuno-checkpoint blockade, the cell cycle, cell apoptosis, key enzymes, c-Met, mTOR signaling and insulin-like growth factor receptors, to exert a stronger anti-tumor effect. An in-depth understanding of the mechanisms that underlie molecular targeted therapies will provide new insights into gastric cancer treatment.

Laser immunotherapy for metastatic pancreatic cancer (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhou, Feifan

2017-02-01

Pancreatic cancer is an extremely malignant disease with high mortality rate. Currently there is no effective therapeutic strategy for highly metastatic pancreatic cancers. Laser immunotherapy (LIT) is a combination therapeutic approach of targeted phototherapy and immunotherapy, which could destroy treated primary tumors with elimination of untreated metastases. LIT affords a remarkable efficacy in suppressing tumor growth in pancreatic tumors in mice, and results in complete tumor regression in many cases. LIT could synergize targeted phototherapy and immunological effects of immunoadjuvant, which represent a promising treatment modality to induce systemic antitumor response through a local intervention, paving the way for the treatment of highly metastatic pancreatic cancers.

Inhalable Magnetic Nanoparticles for Targeted Hyperthermia in Lung Cancer Therapy

PubMed Central

Sadhukha, Tanmoy; Wiedmann, Timothy Scott; Panyam, Jayanth

2015-01-01

Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. PMID:23591395

Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy.

PubMed

Sadhukha, Tanmoy; Wiedmann, Timothy S; Panyam, Jayanth

2013-07-01

Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Esophageal cancer management controversies: Radiation oncology point of view

PubMed Central

Tai, Patricia; Yu, Edward

2014-01-01

Esophageal cancer treatment has evolved from single modality to trimodality therapy. There are some controversies of the role, target volumes and dose of radiotherapy (RT) in the literature over decades. The present review focuses primarily on RT as part of the treatment modalities, and highlight on the RT volume and its dose in the management of esophageal cancer. The randomized adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction. They were randomly assigned to surgery plus postoperative CRT or surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result. Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists. Pre-operative and post-operative target volumes are designed to optimize for disease control. Esophageal brachytherapy is effective in the palliation of dysphagia, but should not be given concomitantly with chemotherapy or external beam RT. The role of brachytherapy in multimodality management requires further investigation. On-going studies of multidisciplinary treatment in locally advanced cancer include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of life analysis). These trials hopefully will shed more light on the future management of esophageal cancer. PMID:25132924

A new methodological approach for PET implementation in radiotherapy treatment planning.

PubMed

Bellan, Elena; Ferretti, Alice; Capirci, Carlo; Grassetto, Gaia; Gava, Marcello; Chondrogiannis, Sotirios; Virdis, Graziella; Marzola, Maria Cristina; Massaro, Arianna; Rubello, Domenico; Nibale, Otello

2012-05-01

In this paper, a new methodological approach to using PET information in radiotherapy treatment planning has been discussed. Computed tomography (CT) represents the primary modality to plan personalized radiation treatment, because it provides the basic electron density map for correct dose calculation. If PET scanning is also performed it is typically coregistered with the CT study. This operation can be executed automatically by a hybrid PET/CT scanner or, if the PET and CT imaging sets have been acquired through different equipment, by a dedicated module of the radiotherapy treatment planning system. Both approaches have some disadvantages: in the first case, the bore of a PET/CT system generally used in clinical practice often does not allow the use of certain bulky devices for patient immobilization in radiotherapy, whereas in the second case the result could be affected by limitations in window/level visualization of two different image modalities, and the displayed PET volumes can appear not to be related to the actual uptake into the patient. To overcome these problems, at our centre a specific procedure has been studied and tested in 30 patients, allowing good results of precision in the target contouring to be obtained. The process consists of segmentation of the biological target volume by a dedicated PET/CT console and its export to a dedicated radiotherapy system, where an image registration between the CT images acquired by the PET/CT scanner and a large-bore CT is performed. The planning target volume is contoured only on the large-bore CT and is used for virtual simulation, to individuate permanent skin markers on the patient.

Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities

DTIC Science & Technology

2011-02-01

Thrombocytopenia, Grade 3 in 1 patient • Hypomagnesemia, Grade 3 in 1 patient • Hypokalemia, Grade 3 in 2 patient • Pneumonia , Grade 3 in 7 patients...urgently needed. While the molecular events involved in lung cancer pathogenesis are being unraveled by ongoing large scale genomics, proteomics, and...tumor initiation, progression and metastasis are an important first step leading to the development of new prognostic markers and targets for therapy

Influence of auditory spatial attention on cross-modal semantic priming effect: evidence from N400 effect.

PubMed

Wang, Hongyan; Zhang, Gaoyan; Liu, Baolin

2017-01-01

Semantic priming is an important research topic in the field of cognitive neuroscience. Previous studies have shown that the uni-modal semantic priming effect can be modulated by attention. However, the influence of attention on cross-modal semantic priming is unclear. To investigate this issue, the present study combined a cross-modal semantic priming paradigm with an auditory spatial attention paradigm, presenting the visual pictures as the prime stimuli and the semantically related or unrelated sounds as the target stimuli. Event-related potentials results showed that when the target sound was attended to, the N400 effect was evoked. The N400 effect was also observed when the target sound was not attended to, demonstrating that the cross-modal semantic priming effect persists even though the target stimulus is not focused on. Further analyses revealed that the N400 effect evoked by the unattended sound was significantly lower than the effect evoked by the attended sound. This contrast provides new evidence that the cross-modal semantic priming effect can be modulated by attention.

SU-E-T-410: Evaluation of Treatment Modalities for Stereotactic Lung Radiation Therapy: A Phantom Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohatt, D; Malhotra, H

Purpose: To evaluate and verify the accuracy of alternative treatment modalities for stereotactic lung therapy with end-to-end testing. We compared three dimensional conformal therapy (3DCRT), dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment using 6 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photons. Methods: A QUASAR respiratory motion phantom was utilized with custom ion chamber and gafchromatic EBT2 film inserts. The phantom contained a low density lung medium with a cylindrical polystyrene tumor (35 cc). Pseudo representative structures for various organs at risk (OAR) were created. Allmore » treatment plans were created using Eclipse ver. 11 using the same image and structure sets, and delivered via Varian TrueBeam STx linear accelerator equipped with high definition MLC. Evaluation of plan quality followed ROTG 0813 criterion for conformity index (CI100%), high dose spillage, D2cm, and R50%. Results: All treatment plans met the OAR dose constraints per protocol and could be delivered without any beam hold offs or other interlocks and hence were deemed clinically safe. For equivalent beam energies, target conformity was improved for all modalities when switching to FFF mode. Treatment efficiency increased for VMAT FFF by a factor of 3–4 over IMRT, and up to factor of 7 when compared to 3DCRT. Pass rates were > 97% for all treatment using gamma criteria of 3%, 3mm. Absolute dose at iso-center was verified with ion chamber, and found to be within 2% of the treatment planning system. Conclusion: The higher dose rate associated with FFF not only reduces delivery times, but in most cases enhances plan quality. The one modality with succeeding best results for all RTOG criterions was VMAT 6 MV FFF. This end-to-end testing provides necessary confidence in the entire dose delivery chain for lung SBRT patients.« less

Targeted radiotherapy with gold nanoparticles: current status and future perspectives

PubMed Central

Ngwa, Wilfred; Kumar, Rajiv; Sridhar, Srinivas; Korideck, Houari; Zygmanski, Piotr; Cormack, Robert A; Berbeco, Ross; Makrigiorgos, G Mike

2014-01-01

Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clinical translation. Future prospects and perspectives are discussed. PMID:24978464

Dosimetric comparison of helical tomotherapy, intensity-modulated radiation therapy, volumetric-modulated arc therapy, and 3-dimensional conformal therapy for the treatment of T1N0 glottic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ekici, Kemal, E-mail: drkemal06@hotmail.com; Pepele, Eda K.; Yaprak, Bahaddin

2016-01-01

Various radiotherapy planning methods for T1N0 laryngeal cancer have been proposed to decrease normal tissue toxicity. We compare helical tomotherapy (HT), linac-based intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and 3-D conformal radiotherapy (3D-CRT) techniques for T1N0 laryngeal cancer. Overall, 10 patients with T1N0 laryngeal cancer were selected and evaluated. Furthermore, 10 radiotherapy treatment plans have been created for all 10 patients, including HT, IMRT, VMAT, and 3D-CRT. IMRT, VMAT, and HT plans vs 3D-CRT plans consistently provided superior planning target volume (PTV) coverage. Similar target coverage was observed between the 3 IMRT modalities. Compared with 3D-CRT, IMRT, HT,more » and VMAT significantly reduced the mean dose to the carotid arteries. VMAT resulted in the lowest mean dose to the submandibular and thyroid glands. Compared with 3D-CRT, IMRT, HT, and VMAT significantly increased the maximum dose to the spinal cord It was observed that the 3 IMRT modalities studied showed superior target coverage with less variation between each plan in comparison with 3D-CRT. The 3D-CRT plans performed better at the D{sub max} of the spinal cord. Clinical investigation is warranted to determine if these treatment approaches would translate into a reduction in radiation therapy–induced toxicities.« less

The small molecule survivin inhibitor YM155 may be an effective treatment modality for colon cancer through increasing apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Wan Lu, E-mail: lvvlchina@msn.cn; Lee, Mi-Ra, E-mail: mira1125@yonsei.ac.kr; Cho, Mee-Yon, E-mail: meeyon@yonsei.ac.kr

Survivin has a known beneficial role in the survival of both cancer cells and normal cells. Therapies targeting survivin have been proposed as an alternative treatment modality for various tumors; however, finding the proper indication for this toxic therapy is critical for reducing unavoidable side effects. We recently observed that high survivin expression in CD133{sup +} cells is related to chemoresistance in Caco-2 colon cancer cells. However, the effect of survivin-targeted therapy on CD133{sup +} colon cancer is unknown. In this study, we investigated the roles of CD133 and survivin expression in colon cancer biology in vitro and comparatively analyzed themore » anticancer effects of survivin inhibitor on CD133{sup +} cells (ctrl-siRNA group) and small interfering RNA (siRNA)-induced CD133{sup −} cells (CD133-siRNA group) obtained from a single colon cancer cell line. CD133 knockdown via siRNA transfection did not change the tumorigenicity of cells, although in vitro survivin expression levels in CD133{sup +} cells were higher than those in siRNA-induced CD133{sup −} cells. The transfection procedure seemed to induce survivin expression. Notably, a significant number of CD133{sup −} cells (33.8%) was found in the cell colonies of the CD133-siRNA group. In the cell proliferation assay after treatment, YM155 and a combination of YM155 and 5-fluorouracil (5-FU) proved to be far more effective than 5-FU alone. A significantly increased level of apoptosis was observed with increasing doses of YM155 in all groups. However, significant differences in therapeutic effect and apoptosis among the mock, ctrl-siRNA, and CD133-siRNA groups were not detected. Survivin inhibitor is an effective treatment modality for colon cancer; however, the role of CD133 and the use of survivin expression as a biomarker for this targeted therapy must be verified.« less

Tracked 3D ultrasound in radio-frequency liver ablation

NASA Astrophysics Data System (ADS)

Boctor, Emad M.; Fichtinger, Gabor; Taylor, Russell H.; Choti, Michael A.

2003-05-01

Recent studies have shown that radio frequency (RF) ablation is a simple, safe and potentially effective treatment for selected patients with liver metastases. Despite all recent therapeutic advancements, however, intra-procedural target localization and precise and consistent placement of the tissue ablator device are still unsolved problems. Various imaging modalities, including ultrasound (US) and computed tomography (CT) have been tried as guidance modalities. Transcutaneous US imaging, due to its real-time nature, may be beneficial in many cases, but unfortunately, fails to adequately visualize the tumor in many cases. Intraoperative or laparoscopic US, on the other hand, provides improved visualization and target imaging. This paper describes a system for computer-assisted RF ablation of liver tumors, combining navigational tracking of a conventional imaging ultrasound probe to produce 3D ultrasound imaging with a tracked RF ablation device supported by a passive mechanical arm and spatially registered to the ultrasound volume.

Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

PubMed

Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

2013-10-01

Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.

IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

DTIC Science & Technology

2015-02-01

Summary of Research Findings This aim was completed as previously reported. DRP-1: Treatment of Malignant Pleural Effusion with ZD6474, a Novel VEGFR...Report: Reporting Period 15 February 2014 – 14 February 2015 Recurrent malignant pleural effusion is a debilitating clinical problem that requires...palliation with repeated therapeutic thoracentesis or pleurodesis (Putnam, J Surg Clin North Am 2002). Malignant pleural effusions have been

Quantitative Image Informatics for Cancer Research (QIICR) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Imaging has enormous untapped potential to improve cancer research through software to extract and process morphometric and functional biomarkers. In the era of non-cytotoxic treatment agents, multi- modality image-guided ablative therapies and rapidly evolving computational resources, quantitative imaging software can be transformative in enabling minimally invasive, objective and reproducible evaluation of cancer treatment response. Post-processing algorithms are integral to high-throughput analysis and fine- grained differentiation of multiple molecular targets.

Delivery of therapeutics using nanocarriers for targeting cancer cells and cancer stem cells.

PubMed

Krishnamurthy, Sangeetha; Ke, Xiyu; Yang, Yi Yan

2015-01-01

Development of cancer resistance, cancer relapse and metastasis are attributed to the presence of cancer stem cells (CSCs). Eradication of this subpopulation has been shown to increase life expectancy of patients. Since the discovery of CSCs a decade ago, several strategies have been devised to specifically target them but with limited success. Nanocarriers have recently been employed to deliver anti-CSC therapeutics for reducing the population of CSCs at the tumor site with great success. This review discusses the different therapeutic strategies that have been employed using nanocarriers, their advantages, success in targeting CSCs and the challenges that are to be overcome. Exploiting this new modality of cancer treatment in the coming decade may improve outcomes profoundly with promise of effective treatment response and reducing relapse and metastasis.

Pathways and therapeutic targets in melanoma

PubMed Central

Shtivelman, Emma; Davies, Michael A.; Hwu, Patrick; Yang, James; Lotem, Michal; Oren, Moshe; Flaherty, Keith T.; Fisher, David E.

2014-01-01

This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments. Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis. This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other “omics”) scale analyses of tumors. The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research. The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy. PMID:24743024

Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection.

PubMed

Sadekar, S; Figueroa, I; Tabrizi, M

2015-07-01

Antibody drug conjugates (ADCs) are a multi-component modality comprising of an antibody targeting a cell-specific antigen, a potent drug/payload, and a linker that can be processed within cellular compartments to release payload upon internalization. Numerous ADCs are being evaluated in both research and clinical settings within the academic and pharmaceutical industry due to their ability to selectively deliver potent payloads. Hence, there is a clear need to incorporate quantitative approaches during early stages of drug development for effective modality design and target selection. In this review, we describe a quantitative approach and framework for evaluation of the interplay between drug- and systems-dependent properties (i.e., target expression, density, localization, turnover, and affinity) in order to deliver a sufficient amount of a potent payload into the relevant target cells. As discussed, theoretical approaches with particular considerations given to various key properties for the target and modality suggest that delivery of the payload into particular effect cells to be more sensitive to antigen concentrations for targets with slow turnover rates as compared to those with faster internalization rates. Further assessments also suggest that increasing doses beyond the threshold of the target capacity (a function of target internalization and expression) may not impact the maximum amount of payload delivered to the intended effect cells. This article will explore the important application of quantitative sciences in selection of the target and design of ADC modalities.

Immunotherapy for lung cancer: advances and prospects.

PubMed

Yang, Li; Wang, Liping; Zhang, Yi

2016-01-01

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

Which technology to select for primary focal treatment of prostate cancer?-European Section of Urotechnology (ESUT) position statement.

PubMed

Ganzer, Roman; Arthanareeswaran, Vinodh Kumar Adithyaa; Ahmed, Hashim U; Cestari, Andrea; Rischmann, Pascal; Salomon, Georg; Teber, Dogu; Liatsikos, Evangelos; Stolzenburg, Jens-Uwe; Barret, Eric

2018-05-09

With growing interest in focal therapy (FT) of prostate cancer (PCa) there is an increasing armamentarium of treatment modalities including high-intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE), vascular targeted photodynamic therapy (VTP), focal brachytherapy (FBT) and stereotactic ablative radiotherapy (SABR). Currently there are no clear recommendations as to which of these technologies are appropriate for individual patient characteristics. Our intention was to review the literature for special aspects of the different technologies that might be of advantage depending on individual patient and tumour characteristics. The current literature on FT was screened for the following factors: morbidity, repeatability, tumour risk category, tumour location, tumour size and prostate volume and anatomical issues. The ESUT expert panel arrived at consensus regarding a position statement on a structured pathway for available FT technologies based on a combination of the literature and expert opinion. Side effects were low across different studies and FT modalities with urinary continence rates of 90-100% and erectile dysfunction between 5 and 52%. Short to medium cancer control based on post-treatment biopsies were variable between ablative modalities. Expert consensus suggested that posterior lesions are better amenable to FT using HIFU. Cryotherapy provides best possible outcomes for anterior tumours. Apical lesions, when treated with FBT, may yield the least urethral morbidity. Further prospective trials are required to assess medium to long term disease control of different ablative modalities for FT. Amongst different available FT modalities our ESUT expert consensus suggests that some may be better for diffe`rent tumour locations. Tumour risk, tumour size, tumour location, and prostate volume are all important factors to consider and might aid in designing future FT trials.

Overview and recent advances in the treatment of neuroblastoma.

PubMed

Whittle, Sarah B; Smith, Valeria; Doherty, Erin; Zhao, Sibo; McCarty, Scott; Zage, Peter E

2017-04-01

Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.

Central and Peripheral Molecular Targets for Anti-Obesity Pharmacotherapy

PubMed Central

Valentino, Michael A.; Lin, Jieru E.; Waldman, Scott A.

2011-01-01

Obesity has emerged as one of the principle worldwide health concerns of the modern era, and there exists a tremendous unmet clinical need for safe and effective therapies to combat this global pandemic. The prevalence of obesity and its associated co-morbidities, including cardiovascular and metabolic diseases, has focused drug discovery and development on generating effective modalities for the treatment and prevention of obesity. Early efforts in the field of obesity pharmacotherapy centered on agents with indeterminate mechanisms of action producing treatment paradigms characterized by significant off-target effects. During the past two decades, new insights have been made into the physiologic regulation of energy balance and the subordinate central and peripheral circuits coordinating appetite, metabolism, and lipogenesis. These studies have revealed previously unrecognized molecular targets for controlling appetite and managing weight from which has emerged a new wave of targeted pharmacotherapies to prevent and control obesity. PMID:20445536

The nitric oxide pathway and possible therapeutic options in pre-eclampsia.

PubMed

Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

2014-08-01

Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide-soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3',5'-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. © 2013 The British Pharmacological Society.

The nitric oxide pathway and possible therapeutic options in pre-eclampsia

PubMed Central

Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

2014-01-01

Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide–soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3′,5′-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

Neural network for intelligent query of an FBI forensic database

NASA Astrophysics Data System (ADS)

Uvanni, Lee A.; Rainey, Timothy G.; Balasubramanian, Uma; Brettle, Dean W.; Weingard, Fred; Sibert, Robert W.; Birnbaum, Eric

1997-02-01

Examiner is an automated fired cartridge case identification system utilizing a dual-use neural network pattern recognition technology, called the statistical-multiple object detection and location system (S-MODALS) developed by Booz(DOT)Allen & Hamilton, Inc. in conjunction with Rome Laboratory. S-MODALS was originally designed for automatic target recognition (ATR) of tactical and strategic military targets using multisensor fusion [electro-optical (EO), infrared (IR), and synthetic aperture radar (SAR)] sensors. Since S-MODALS is a learning system readily adaptable to problem domains other than automatic target recognition, the pattern matching problem of microscopic marks for firearms evidence was analyzed using S-MODALS. The physics; phenomenology; discrimination and search strategies; robustness requirements; error level and confidence level propagation that apply to the pattern matching problem of military targets were found to be applicable to the ballistic domain as well. The Examiner system uses S-MODALS to rank a set of queried cartridge case images from the most similar to the least similar image in reference to an investigative fired cartridge case image. The paper presents three independent tests and evaluation studies of the Examiner system utilizing the S-MODALS technology for the Federal Bureau of Investigation.

Policy and administrative issues for large-scale clinical interventions following disasters.

PubMed

Scheeringa, Michael S; Cobham, Vanessa E; McDermott, Brett

2014-02-01

Large, programmatic mental health intervention programs for children and adolescents following disasters have become increasingly common; however, little has been written about the key goals and challenges involved. Using available data and the authors' experiences, this article reviews the factors involved in planning and implementing large-scale treatment programs following disasters. These issues include funding, administration, choice of clinical targets, workforce selection, choice of treatment modalities, training, outcome monitoring, and consumer uptake. Ten factors are suggested for choosing among treatment modalities: 1) reach (providing access to the greatest number), 2) retention of patients, 3) privacy, 4) parental involvement, 5) familiarity of the modality to clinicians, 6) intensity (intervention type matches symptom acuity and impairment of patient), 7) burden to the clinician (in terms of time, travel, and inconvenience), 8) cost, 9) technology needs, and 10) effect size. Traditionally, after every new disaster, local leaders who have never done so before have had to be recruited to design, administer, and implement programs. As expertise in all of these areas represents a gap for most local professionals in disaster-affected areas, we propose that a central, nongovernmental agency with national or international scope be created that can consult flexibly with local leaders following disasters on both overarching and specific issues. We propose recommendations and point out areas in greatest need of innovation.

Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer.

PubMed

Guo, Ranran; Peng, Haibao; Tian, Ye; Shen, Shun; Yang, Wuli

2016-09-01

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dose- and LET-painting with particle therapy.

PubMed

Bassler, Niels; Jäkel, Oliver; Søndergaard, Christian Skou; Petersen, Jørgen B

2010-10-01

Tumour hypoxia is one of the limiting factors in obtaining tumour control in radiotherapy. The high-LET region of a beam of heavy charged particles such as carbon ions is located in the distal part of the Bragg peak. A modulated or spread out Bragg peak (SOBP) is a weighted function of several Bragg peaks at various energies, which however results in a dilution of the dose-average LET in the target volume. Here, we investigate the possibility to redistribute the LET by dedicated treatment plan optimisation, in order to maximise LET in the target volume. This may be a strategy to potentially overcome hypoxia along with dose escalation or dose painting. The high-LET region can be shaped in very different ways, while maintaining the distribution of the absorbed dose or biological effective dose. Treatment plans involving only carbon ion beams, show very different LET distributions depending on how the fields are arranged. Alternatively, a LET boost can be applied in multi-modal treatment planning, such as combining carbon ions with protons and/or photons. For such mixed radiation modalities, significant "LET boosts" can be achieved at nearly arbitrary positions within the target volume. Following the general understanding of the relationship between hypoxia, LET and the oxygen enhancement ratio (OER), we conclude, that an additional therapeutic advantage can be achieved by confining the high-LET part of the radiation in hypoxic compartments of the tumour, and applying low-LET radiation to the normoxic tissue. We also anticipate that additional advantages may be achieved by deliberate sparing of normal tissue from high LET regions. Consequently, treatment planning based on simultaneous dose and LET optimisation has a potential to achieve higher tumour control and/or reduced normal tissue control probability (NTCP).

MO-AB-BRA-02: A Novel Scatter Imaging Modality for Real-Time Image Guidance During Lung SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redler, G; Bernard, D; Templeton, A

2015-06-15

Purpose: A novel scatter imaging modality is developed and its feasibility for image-guided radiation therapy (IGRT) during stereotactic body radiation therapy (SBRT) for lung cancer patients is assessed using analytic and Monte Carlo models as well as experimental testing. Methods: During treatment, incident radiation interacts and scatters from within the patient. The presented methodology forms an image of patient anatomy from the scattered radiation for real-time localization of the treatment target. A radiographic flat panel-based pinhole camera provides spatial information regarding the origin of detected scattered radiation. An analytical model is developed, which provides a mathematical formalism for describing themore » scatter imaging system. Experimental scatter images are acquired by irradiating an object using a Varian TrueBeam accelerator. The differentiation between tissue types is investigated by imaging simple objects of known compositions (water, lung, and cortical bone equivalent). A lung tumor phantom, simulating materials and geometry encountered during lung SBRT treatments, is fabricated and imaged to investigate image quality for various quantities of delivered radiation. Monte Carlo N-Particle (MCNP) code is used for validation and testing by simulating scatter image formation using the experimental pinhole camera setup. Results: Analytical calculations, MCNP simulations, and experimental results when imaging the water, lung, and cortical bone equivalent objects show close agreement, thus validating the proposed models and demonstrating that scatter imaging differentiates these materials well. Lung tumor phantom images have sufficient contrast-to-noise ratio (CNR) to clearly distinguish tumor from surrounding lung tissue. CNR=4.1 and CNR=29.1 for 10MU and 5000MU images (equivalent to 0.5 and 250 second images), respectively. Conclusion: Lung SBRT provides favorable treatment outcomes, but depends on accurate target localization. A comprehensive approach, employing multiple simulation techniques and experiments, is taken to demonstrate the feasibility of a novel scatter imaging modality for the necessary real-time image guidance.« less

ErbB-targeted CAR T-cell immunotherapy of cancer.

PubMed

Whilding, Lynsey M; Maher, John

2015-01-01

Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

Continuation of Weight Loss Treatment Is Associated with the Number of Self-Selected Treatment Modalities

ERIC Educational Resources Information Center

Martin, Corby K.; Drab-Hudson, Danae L.; York-Crowe, Emily; Mayville, Stephen B.; Yu, Ying; Greenway, Frank L.

2007-01-01

Behavior therapy is a cornerstone of weight loss treatment and behaviorists help direct patients' treatment. A novel design was used that allowed participants to choose different treatment modalities during behavioral weight loss treatment. The association between the selection of different treatment modalities and program completion was examined…

Development of novel therapies for MG: Studies in animal models.

PubMed

Souroujon, M C; Brenner, T; Fuchs, S

2010-08-01

Experimental myasthenia gravis (MG) in animals, and in particular experimental autoimmune MG in rodents, serves as excellent models to study possible novel therapeutic modalities for MG. The current treatments for MG are based on cholinesterase inhibitors, general immunosuppressants, and corticosteroids, broad immunomodulatory therapies such as plasma exchange or intravenous immunoglobulins (IVIGs), and thymectomy for selected patients. This stresses the need for immunotherapies that would specifically or preferentially suppress the undesirable autoimmune response without widely affecting the entire immune system as most available treatments do. The available animal models for MG enable to perform preclinical studies in which novel therapeutic approaches can be tested. In this review, we describe the different therapeutic approaches that were so far tested in experimental models of MG and discuss their underlying mechanisms of action. These include antigen - acetylcholine receptor (AChR)-dependent treatments aimed at specifically abrogating the humoral and cellular anti-AChR responses as well as immunomodulatory approaches that could be used either alone or in conjunction with antigen-specific treatments or alternatively serve as steroid sparing agents. The antigen-specific treatments are based on fragments or peptides derived from the acetylcholine receptor (AChR) that would theoretically deviate the anti-AChR autoimmune response away from the muscle target or on ways to target AChR-specific T- and B- cell responses or antibodies. The immunomodulatory modalities include cell-based and non-cell-based ways to affect or manipulate key players in the autoimmune process such as regulatory T cells, dendritic cells, cytokine networks, and chemokine and costimulatory signaling as well as complement pathways. We also describe approaches that attempt to affect the cholinergic balance, which is impaired at the neuromuscular junction. In addition to enabling to test the feasibility of novel approaches, experimental MG enables to perform analyses of existing treatment modalities, which cannot be performed in human MG patients. These include studies on the mode of action of various immunosuppressants and on IVIGs. Hopefully, the vast repertoire of therapeutic approaches that are studied in experimental models of MG will pave the way to clinical studies that will eventually improve the management of MG.

Gene therapy for carcinoma of the breast

PubMed Central

Stoff-Khalili, MA; Dall, P; Curiel, DT

2007-01-01

In view of the limited success of available treatment modalities for breast cancer, alternative and complementary strategies need to be developed. The delineation of the molecular basis of breast cancer provides the possibility of specific intervention by gene therapy through the introduction of genetic material for therapeutic purposes. In this regard, several gene therapy approaches for carcinoma of the breast have been developed. These approaches can be divided into six broad categories: (1) mutation compensation, (2) molecular chemotherapy, (3) proapoptotic gene therapy, (4) antiangiogenic gene therapy, (5) genetic immunopotentiation, and (6) genetic modulation of resistance/sensitivity. Clinical trials for breast cancer have been initiated to evaluate safety, toxicity, and efficacy. Combined modality therapy with gene therapy and chemotherapy or radiation therapy has shown promising results. It is expected that as new therapeutic targets and approaches are identified and advances in vector design are realized, gene therapy will play an increasing role in clinical breast cancer treatment. PMID:16410823

Current concepts for the combined treatment modality of ionizing radiation with anticancer agents.

PubMed

Oehler, Christoph; Dickinson, Daniel J; Broggini-Tenzer, Angela; Hofstetter, Barbara; Hollenstein, Andreas; Riesterer, Oliver; Vuong, Van; Pruschy, Martin

2007-01-01

In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's.

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals.more » Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mwidu, U; Devic, S; Shehadeh, M

Purpose: A retrospective comparison of dose distributions achievable by High dose rate brachytherapy (HDRBT), Helical TomoTherapy (TOMO), CyberKnife (CK) and RapidArc (RA) in locally advanced inoperable cervical cancer patients is presented. Methods: Five patients with advanced stage cervical carcinoma were selected for this study after a full course of external beam radiotherapy (EBRT), chemotherapy and HDR Brachytherapy. To highlight any significant similarities/differences in dose distributions, high-risk clinical target volume (HRCTV) coverage, organs at risk (OAR) sparing, and machine specific delivery limitations, we used D90 (dose received by 90% of the volume) as the parameter for HRCTV coverage as recommended bymore » the GEC-ESTRO Working Group. We also compared both integral and differential dose volume histograms (DVH) between different dose distributions treatment modalities for HRCTV and OAR. Results: TOMO and RA provided the most conformal dose distributions to HRCTV. Median doses (in Gy) to organs at risk were; for rectal wall: 1.7±0.6, 2.5±0.6,1.2±0.3, and 1.5±0.6, and for bladder wall: 1.6±0.1, 2.4±0.4, 0.8±0.6, and 1.5±0.5, for HDRBT, TOMO, CK, and RA, respectively. Conclusion: Contemporary EBRT modalities might be able to replace brachytherapy treatments for cervix cancer. While brachytherapy dose distributions feature high dose gradients, EBRT modalities provide highly conformal dose distributions to the target. However, it is still not clear whether a highly conformal dose or high gradient dose is more clinically relevant for the HRCTV in cervix cancer patients.« less

Prostate Stem Cell Antigen: A Prospective Therapeutic and Diagnostic Target

PubMed Central

Raff, Adam B.; Gray, Andrew; Kast, W. Martin

2009-01-01

The development of novel clinical tools to combat cancer is an intense field of research and recent efforts have been directed at the identification of proteins that may provide diagnostic, prognostic and/or therapeutic applications due to their restricted expression. To date, a number of protein candidates have emerged as potential clinical tools in the treatment of prostate cancer. Discovered over ten year ago, prostate stem cell antigen (PSCA) is a cell surface antigen that belongs to the Ly-6/Thy-1 family of glycosylphosphatidylinositol-anchored proteins. PSCA is highly overexpressed in human prostate cancer, with limited expression in normal tissues, making it an ideal target for both diagnosis and therapy. Several studies have now clearly correlated the expression of PSCA with relevant clinical benchmarks, such as Gleason score and metastasis, while others have demonstrated the efficacy of PSCA targeting in treatment through various modalities. The purpose of this review is to present the current body of knowledge about PSCA and its potential role in the treatment of human prostate cancer. PMID:18838214

[Homozygous familial hypercholesterolemia].

PubMed

Kayikçioğlu, Meral

2014-10-01

Familial hypercholesterolemia (FH) is caused by genetic deficiency of LDL receptors leading to extremely high cholesterol levels and atherosclerosis at early ages. For the prevention of early atherosclerotic cardiovascular events, effective reduction of LDL-cholesterol is necessary from the early ages. However, particularly in homozygous patients, it's almost impossible to achieve target LDL-cholesterol levels with antilipid agents including statin agents, due to the severe LDL receptor dysfunction. LDL apheresis is an effective treatment modality in severe AH patients. However, the invasive, chronic time consuming nature of this treatment decreases the compliance of these patients. Moreover, atherosclerosis progress in 25% of the patients undergoing regular and effective apheresis even though since early ages. Clinical data also indicate that there is still an unmet medical need for new effective treatments for AH patients. This review will address new therapeutic strategies targeting Apolipoprotein (Apo) B including MTTP inhibitor Lomitapideand oligonucleotide Mipomersen. As both agents are targeted against ApoB, they are expected to be effective even in receptor negative homozygous AH patients.

Novel and Experimental Therapies in Chronic Pancreatitis.

PubMed

Jagannath, Soumya; Garg, Pramod Kumar

2017-07-01

Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas. The currently available treatment of CP is aimed at controlling symptoms and managing complications. Unfortunately, no specific treatment is available to halt the progression of the disease process because the pathophysiological perturbations in CP are not well understood. In this review, we discuss various therapeutic targets and investigational agents acting on these targets. Among these, therapies modulating immune cells and those acting on pancreatic stellate cells appear promising and may translate into clinical benefit in near future. However, these experimental therapies are mostly in animal models and they do not recapitulate all aspects of human disease. Still they may be beneficial in developing effective therapeutic modalities to curb inflammation in chronic pancreatitis.

The Danish Centre for Strategic Research in Type 2 Diabetes (DD2) study: expected outcome from the DD2 project and two intervention studies

PubMed Central

Beck-Nielsen, Henning; Solomon, Thomas PJ; Lauridsen, Jørgen; Karstoft, Kristian; Pedersen, Bente K; Johnsen, Søren P; Nielsen, Jens Steen; Kryger, Tine Bjerregaard; Sortsø, Camilla; Vaag, Allan

2012-01-01

The overall aim of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) is to near-normalize metabolic control in newly diagnosed patients with type 2 diabetes (T2D) using an individualized treatment approach. We hypothesize that this will not only prevent complications and improve quality of life for T2D patients but also result in increased cost efficiency compared with current treatment modalities. This paper provides an overview of the expected outcomes from DD2, focusing on the two main intervention studies. The main data for the DD2 project are collected during patient enrollment and stored using the individual civil registration number. This enables subsequent linking to other national databases where supplemental data can be obtained. All data will be used for designing treatment guidelines and continuously monitoring the development of diabetic complications, thereby obtaining knowledge about predictors for the long-term outcome and identifying targets for new interventions. Further data are being collected from two intervention studies. The aim of the first intervention study is to improve T2D treatment using an individualized treatment modality optimizing medication according to individual metabolic responses and phenotypic characteristics. The aim of the second intervention study is to develop an evidence-based training protocol to be implemented as a treatment modality for T2D and used for initiating lifelong changes in physical activity levels in patients with T2D. An initial pilot study evaluating an interval-based walking protocol is ongoing, and preliminary results indicate that this protocol is an optimal “free-living” training intervention. An initial health-economic analysis will also be performed as a basis for analysis of the data collected during the project. A cost-benefit analysis of the two intervention studies will be conducted. The DD2 project is expected to lead to improved treatment modalities and increased knowledge about existing treatment guidelines, and will also provide a solid base for health-economic decision-making. PMID:23071408

An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

PubMed

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-09-21

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

A study of the radiobiological modeling of the conformal radiation therapy in cancer treatment

NASA Astrophysics Data System (ADS)

Pyakuryal, Anil Prasad

Cancer is one of the leading causes of mortalities in the world. The precise diagnosis of the disease helps the patients to select the appropriate modality of the treatments such as surgery, chemotherapy and radiation therapy. The physics of X-radiation and the advanced imaging technologies such as positron emission tomography (PET) and computed tomography (CT) plays an important role in the efficient diagnosis and therapeutic treatments in cancer. However, the accuracy of the measurements of the metabolic target volumes (MTVs) in the PET/CT dual-imaging modality is always limited. Similarly the external beam radiation therapy (XRT) such as 3D conformal radiotherapy (3DCRT) and intensity modulated radiation therapy (IMRT) is the most common modality in the radiotherapy treatment. These treatments are simulated and evaluated using the XRT plans and the standard methodologies in the commercial planning system. However, the normal organs are always susceptible to the radiation toxicity in these treatments due to lack of knowledge of the appropriate radiobiological models to estimate the clinical outcomes. We explored several methodologies to estimate MTVs by reviewing various techniques of the target volume delineation using the static phantoms in the PET scans. The review suggests that the more precise and practical method of delineating PET MTV should be an intermediate volume between the volume coverage for the standardized uptake value (SUV; 2.5) of glucose and the 50% (40%) threshold of the maximum SUV for the smaller (larger) volume delineations in the radiotherapy applications. Similarly various types of optimal XRT plans were designed using the CT and PET/CT scans for the treatment of various types of cancer patients. The qualities of these plans were assessed using the universal plan-indices. The dose-volume criteria were also examined in the targets and organs by analyzing the conventional dose-volume histograms (DVHs). The biological models such as tumor control probability based on Poisson statistics model, and normal tissue complication probabilities based on Lyman-Kutcher-Burman model, were efficient to estimate the radiobiological outcomes of the treatments by taking into account of the dose-volume effects in the organs. Furthermore, a novel technique of spatial DVH analysis was also found to be useful to determine the primary cause of the complications in the critical organs in the treatments. The study also showed that the 3DCRT and IMRT techniques offer the promising results in the XRT treatment of the left-breast and the prostate cancer patients respectively. Unfortunately, several organs such as salivary glands and larynx, and esophagus, were found to be significantly vulnerable to the radiation toxicity in the treatment of the head and neck (HN), and left-lung cancer patients respectively. The radiobiological outcomes were also found to be consistent with the clinical results of the IMRT based treatments of a significant number of the HN cancer patients.

Evolution of multidisciplinary brain metastasis management: case study and literature review.

PubMed

Colaco, Rovel; Martin, Pierre; Chiang, Veronica

2015-06-01

Up to 40 percent of all cancer patients develop brain metastasis (BM) during the course of their disease. Despite advances in diagnosis and therapy, prognosis in patients with BM remains poor for many patients, but for some, survival can be of the order of several years in duration. Difficulty in predicting long-term survivors has created controversy in contemporary management of BM. Minimizing medical and neurocognitive side effects (disease borne or iatrogenic) to enhance functional independence and improving overall quality of life in these individuals requires a coordinated approach of first-line and salvage surgical, chemotherapeutic (cytotoxic, targeted, or immune based), and radiation (whole brain radiotherapy or stereotactic radiosurgery) modalities. This goal needs to be balanced against the more traditional targets of management such as symptom relief, reducing tumor burden, and local tumor control, thereby increasing progression-free survival. This case study and literature review demonstrates the role of various treatment modalities in the management of BM.

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

PubMed

Chan, Maria F; Song, Yulin; Burman, Chandra; Chui, Chen S; Schupak, Karen

2006-01-01

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

PET/CT aids the staging of and radiotherapy planning for early-stage extranodal natural killer/T-cell lymphoma, nasal type: A case series

PubMed Central

2011-01-01

Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare form of non-Hodgkin lymphoma. Treatment of ENKTL primarily relies on radiation; thus, proper delineation of target volumes is critical. Currently, the ideal modalities for delineation of gross tumor volume for ENKTL are unknown. We describe three consecutive cases of localized ENKTL that presented to the Nova Scotia Cancer Centre in Halifax, Nova Scotia. All patients had a planning CT and MRI as well as a planning FDG-PET/CT in the radiotherapy treatment position, wearing immobilization masks. All patients received radiation alone. In two patients, PET/CT changed not only the stage, but also the target volume requiring treatment. The third patient was unable to tolerate an MRI, but was able to undergo PET/CT, which improved the accuracy of the target volume. PET/CT aided the staging of and radiotherapy planning for our patients and appears to be a promising tool in the treatment of ENKTL. PMID:22208903

Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications

NASA Astrophysics Data System (ADS)

Sun, Lining; Wei, Zuwu; Chen, Haige; Liu, Jinliang; Guo, Jianjian; Cao, Ming; Wen, Tieqiao; Shi, Liyi

2014-07-01

Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents. Electronic supplementary information (ESI) available: Up-conversion luminescence spectra of UCNC-Er and UCNC-Er-FA, UCNC-Tm and UCNC-Tm-FA. Confocal luminescence imaging data collected as a series along the Z optical axis. See DOI: 10.1039/c4nr02312a

Monte Carlo simulations of patient dose perturbations in rotational-type radiotherapy due to a transverse magnetic field: A tomotherapy investigation

PubMed Central

Yang, Y. M.; Geurts, M.; Smilowitz, J. B.; Sterpin, E.; Bednarz, B. P.

2015-01-01

Purpose: Several groups are exploring the integration of magnetic resonance (MR) image guidance with radiotherapy to reduce tumor position uncertainty during photon radiotherapy. The therapeutic gain from reducing tumor position uncertainty using intrafraction MR imaging during radiotherapy could be partially offset if the negative effects of magnetic field-induced dose perturbations are not appreciated or accounted for. The authors hypothesize that a more rotationally symmetric modality such as helical tomotherapy will permit a systematic mediation of these dose perturbations. This investigation offers a unique look at the dose perturbations due to homogeneous transverse magnetic field during the delivery of Tomotherapy® Treatment System plans under varying degrees of rotational beamlet symmetry. Methods: The authors accurately reproduced treatment plan beamlet and patient configurations using the Monte Carlo code geant4. This code has a thoroughly benchmarked electromagnetic particle transport physics package well-suited for the radiotherapy energy regime. The three approved clinical treatment plans for this study were for a prostate, head and neck, and lung treatment. The dose heterogeneity index metric was used to quantify the effect of the dose perturbations to the target volumes. Results: The authors demonstrate the ability to reproduce the clinical dose–volume histograms (DVH) to within 4% dose agreement at each DVH point for the target volumes and most planning structures, and therefore, are able to confidently examine the effects of transverse magnetic fields on the plans. The authors investigated field strengths of 0.35, 0.7, 1, 1.5, and 3 T. Changes to the dose heterogeneity index of 0.1% were seen in the prostate and head and neck case, reflecting negligible dose perturbations to the target volumes, a change from 5.5% to 20.1% was observed with the lung case. Conclusions: This study demonstrated that the effect of external magnetic fields can be mitigated by exploiting a more rotationally symmetric treatment modality. PMID:25652485

Emerging drugs for the treatment of wound healing.

PubMed

Zielins, Elizabeth R; Brett, Elizabeth A; Luan, Anna; Hu, Michael S; Walmsley, Graham G; Paik, Kevin; Senarath-Yapa, Kshemendra; Atashroo, David A; Wearda, Taylor; Lorenz, H Peter; Wan, Derrick C; Longaker, Michael T

2015-06-01

Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process. A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed. The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

Radiotherapy treatment planning: benefits of CT-MR image registration and fusion in tumor volume delineation.

PubMed

Djan, Igor; Petrović, Borislava; Erak, Marko; Nikolić, Ivan; Lucić, Silvija

2013-08-01

Development of imaging techniques, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), made great impact on radiotherapy treatment planning by improving the localization of target volumes. Improved localization allows better local control of tumor volumes, but also minimizes geographical misses. Mutual information is obtained by registration and fusion of images achieved manually or automatically. The aim of this study was to validate the CT-MRI image fusion method and compare delineation obtained by CT versus CT-MRI image fusion. The image fusion software (XIO CMS 4.50.0) was applied to delineate 16 patients. The patients were scanned on CT and MRI in the treatment position within an immobilization device before the initial treatment. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on CT alone and on CT+MRI images consecutively and image fusion was obtained. Image fusion showed that CTV delineated on a CT image study set is mainly inadequate for treatment planning, in comparison with CTV delineated on CT-MRI fused image study set. Fusion of different modalities enables the most accurate target volume delineation. This study shows that registration and image fusion allows precise target localization in terms of GTV and CTV and local disease control.

Treatment of early non-small cell lung cancer, stage IA, by image-guided robotic stereotactic radioablation--CyberKnife.

PubMed

Brown, William T; Wu, Xiaodong; Amendola, Beatriz; Perman, Mark; Han, Hoke; Fayad, Fahed; Garcia, Silvio; Lewin, Alan; Abitbol, Andre; de la Zerda, Alberto; Schwade, James G

2007-01-01

To evaluate the efficacy of using image-guided robotic stereotactic radioablation as an alternative treatment modality for patients with surgically resectable, but medically inoperable, T1 N0 M0, stage IA non-small cell lung cancer. Between January 2004 and May 2006, 19 patients, 11 women and 8 men ranging in age from 52 to 88 years, with stage IA non-small cell lung cancer were treated. Tumor volume ranged from 1.7 to 13 mL. Total doses ranged from 24 to 60 Gy delivered in 3 fractions. Eleven patients received 60 Gy. Real-time target localization was accomplished by radiographic detection of fiducial marker(s) implanted within the tumor combined with respiratory motion tracking. All patients tolerated radioablation well with fatigue as the main side effect. Fourteen patients are alive from 1 to 25 months posttreatment. Four patients died: 2 of comorbid disease and 2 of cancer progression (status post 60 and 55.5 Gy). Three patients developed grade I radiation pneumonitis. Two patients have stable disease. In 3 patients, cancer recurred in the planning treatment volume: in 2 patients after treatment with 60 Gy and in 1 patient after treatment with 55.5 Gy. One patient had local control in the target volume but developed metastasis to the ipsilateral hilum. Nine patients had a complete response and show no evidence of disease. In our early experience, stereotactic radioablation using the CyberKnife system appears to be a safe, minimally invasive, and effective modality for treating early stage lung cancer in patients with medically inoperable disease. Dose escalation and/or increasing the treatment volumes, with the aid of the high conformality of this technique, may help to achieve further improvements in these promising results.

Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma.

PubMed

Sekido, Yoshitaka

2018-03-22

Malignant mesothelioma (MM) constitutes a very aggressive tumor that arises from the pleural or peritoneal cavities and is highly refractory to conventional therapies. Several key genetic alterations are associated with the development and progression of MM including mutations of the CDKN2A/ARF , NF2 , and BAP1 tumor-suppressor genes. Notably, activating oncogene mutations are very rare; thus, it is difficult to develop effective inhibitors to treat MM. The NF2 gene encodes merlin, a protein that regulates multiple cell-signaling cascades including the Hippo pathway. MMs also exhibit inactivation of Hippo pathway components including LATS1/2, strongly suggesting that merlin-Hippo pathway dysregulation plays a key role in the development and progression of MM. Furthermore, Hippo pathway inactivation has been shown to result in constitutive activation of the YAP1/TAZ transcriptional coactivators, thereby conferring malignant phenotypes to mesothelial cells. Critical YAP1/TAZ target genes, including prooncogenic CCDN1 and CTGF , have also been shown to enhance the malignant phenotypes of MM cells. Together, these data indicate the Hippo pathway as a therapeutic target for the treatment of MM, and support the development of new strategies to effectively target the activation status of YAP1/TAZ as a promising therapeutic modality for this formidable disease.

Policy and Administrative Issues for Large-Scale Clinical Interventions Following Disasters

PubMed Central

Cobham, Vanessa E.; McDermott, Brett

2014-01-01

Abstract Objective: Large, programmatic mental health intervention programs for children and adolescents following disasters have become increasingly common; however, little has been written about the key goals and challenges involved. Methods: Using available data and the authors' experiences, this article reviews the factors involved in planning and implementing large-scale treatment programs following disasters. Results: These issues include funding, administration, choice of clinical targets, workforce selection, choice of treatment modalities, training, outcome monitoring, and consumer uptake. Ten factors are suggested for choosing among treatment modalities: 1) reach (providing access to the greatest number), 2) retention of patients, 3) privacy, 4) parental involvement, 5) familiarity of the modality to clinicians, 6) intensity (intervention type matches symptom acuity and impairment of patient), 7) burden to the clinician (in terms of time, travel, and inconvenience), 8) cost, 9) technology needs, and 10) effect size. Traditionally, after every new disaster, local leaders who have never done so before have had to be recruited to design, administer, and implement programs. Conclusion: As expertise in all of these areas represents a gap for most local professionals in disaster-affected areas, we propose that a central, nongovernmental agency with national or international scope be created that can consult flexibly with local leaders following disasters on both overarching and specific issues. We propose recommendations and point out areas in greatest need of innovation. PMID:24521227

ADMultiImg: a novel missing modality transfer learning based CAD system for diagnosis of MCI due to AD using incomplete multi-modality imaging data

NASA Astrophysics Data System (ADS)

Liu, Xiaonan; Chen, Kewei; Wu, Teresa; Weidman, David; Lure, Fleming; Li, Jing

2018-02-01

Alzheimer's Disease (AD) is the most common cause of dementia and currently has no cure. Treatments targeting early stages of AD such as Mild Cognitive Impairment (MCI) may be most effective to deaccelerate AD, thus attracting increasing attention. However, MCI has substantial heterogeneity in that it can be caused by various underlying conditions, not only AD. To detect MCI due to AD, NIA-AA published updated consensus criteria in 2011, in which the use of multi-modality images was highlighted as one of the most promising methods. It is of great interest to develop a CAD system based on automatic, quantitative analysis of multi-modality images and machine learning algorithms to help physicians more adequately diagnose MCI due to AD. The challenge, however, is that multi-modality images are not universally available for many patients due to cost, access, safety, and lack of consent. We developed a novel Missing Modality Transfer Learning (MMTL) algorithm capable of utilizing whatever imaging modalities are available for an MCI patient to diagnose the patient's likelihood of MCI due to AD. Furthermore, we integrated MMTL with radiomics steps including image processing, feature extraction, and feature screening, and a post-processing for uncertainty quantification (UQ), and developed a CAD system called "ADMultiImg" to assist clinical diagnosis of MCI due to AD using multi-modality images together with patient demographic and genetic information. Tested on ADNI date, our system can generate a diagnosis with high accuracy even for patients with only partially available image modalities (AUC=0.94), and therefore may have broad clinical utility.

A tri-modality image fusion method for target delineation of brain tumors in radiotherapy.

PubMed

Guo, Lu; Shen, Shuming; Harris, Eleanor; Wang, Zheng; Jiang, Wei; Guo, Yu; Feng, Yuanming

2014-01-01

To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors. A new method of tri-modality image fusion was developed, which can fuse and display all image sets in one panel and one operation. And a feasibility study in gross tumor volume (GTV) delineation using data from three patients with brain tumors was conducted, which included images of simulation CT, MRI, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) examinations before radiotherapy. Tri-modality image fusion was implemented after image registrations of CT+PET and CT+MRI, and the transparency weight of each modality could be adjusted and set by users. Three radiation oncologists delineated GTVs for all patients using dual-modality (MRI/CT) and tri-modality (MRI/CT/PET) image fusion respectively. Inter-observer variation was assessed by the coefficient of variation (COV), the average distance between surface and centroid (ADSC), and the local standard deviation (SDlocal). Analysis of COV was also performed to evaluate intra-observer volume variation. The inter-observer variation analysis showed that, the mean COV was 0.14(± 0.09) and 0.07(± 0.01) for dual-modality and tri-modality respectively; the standard deviation of ADSC was significantly reduced (p<0.05) with tri-modality; SDlocal averaged over median GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm) and patient 3 (from 0.42 cm to 0.36 cm) with the new method. The intra-observer volume variation was also significantly reduced (p = 0.00) with the tri-modality method as compared with using the dual-modality method. With the new tri-modality image fusion method smaller inter- and intra-observer variation in GTV definition for the brain tumors can be achieved, which improves the consistency and accuracy for target delineation in individualized radiotherapy.

Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases

PubMed Central

Geldenhuys, Werner J.; Lin, Li; Darvesh, Altaf S.; Sadana, Prabodh

2017-01-01

Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet. In this review, we present the biology of LPL, highlight the LPL modulation property of currently used drugs and review the novel emerging approaches to target LPL. PMID:27771332

Transient analysis mode participation for modal survey target mode selection using MSC/NASTRAN DMAP

NASA Technical Reports Server (NTRS)

Barnett, Alan R.; Ibrahim, Omar M.; Sullivan, Timothy L.; Goodnight, Thomas W.

1994-01-01

Many methods have been developed to aid analysts in identifying component modes which contribute significantly to component responses. These modes, typically targeted for dynamic model correlation via a modal survey, are known as target modes. Most methods used to identify target modes are based on component global dynamic behavior. It is sometimes unclear if these methods identify all modes contributing to responses important to the analyst. These responses are usually those in areas of hardware design concerns. One method used to check the completeness of target mode sets and identify modes contributing significantly to important component responses is mode participation. With this method, the participation of component modes in dynamic responses is quantified. Those modes which have high participation are likely modal survey target modes. Mode participation is most beneficial when it is used with responses from analyses simulating actual flight events. For spacecraft, these responses are generated via a structural dynamic coupled loads analysis. Using MSC/NASTRAN DMAP, a method has been developed for calculating mode participation based on transient coupled loads analysis results. The algorithm has been implemented to be compatible with an existing coupled loads methodology and has been used successfully to develop a set of modal survey target modes.

DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

PubMed Central

Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

2013-01-01

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

Moving receptor redirected adoptive cell therapy toward fine tuning of antitumor responses.

PubMed

Chicaybam, Leonardo; Bonamino, Martin Hernan

2014-10-01

Adoptive cell transfer (ACT) is emerging as a powerful modality of cancer treatment. While ACT has proved able to induce massive clinical responses, genetic modification of T lymphocytes further improved clinical responses obtained. One of the major current limitations of ACT is the inability to discern healthy from malignant cells, leading to on target/off tumor responses that can limit its application. We here discuss some of the approaches currently under development and potential solutions to circumvent these limitations and extend this potentially curative therapy to different tumors by targeting a variety of antigens.

Multisensory and Modality-Specific Influences on Adaptation to Optical Prisms

PubMed Central

Calzolari, Elena; Albini, Federica; Bolognini, Nadia; Vallar, Giuseppe

2017-01-01

Visuo-motor adaptation to optical prisms displacing the visual scene (prism adaptation, PA) is a method used for investigating visuo-motor plasticity in healthy individuals and, in clinical settings, for the rehabilitation of unilateral spatial neglect. In the standard paradigm, the adaptation phase involves repeated pointings to visual targets, while wearing optical prisms displacing the visual scene laterally. Here we explored differences in PA, and its aftereffects (AEs), as related to the sensory modality of the target. Visual, auditory, and multisensory – audio-visual – targets in the adaptation phase were used, while participants wore prisms displacing the visual field rightward by 10°. Proprioceptive, visual, visual-proprioceptive, auditory-proprioceptive straight-ahead shifts were measured. Pointing to auditory and to audio-visual targets in the adaptation phase produces proprioceptive, visual-proprioceptive, and auditory-proprioceptive AEs, as the typical visual targets did. This finding reveals that cross-modal plasticity effects involve both the auditory and the visual modality, and their interactions (Experiment 1). Even a shortened PA phase, requiring only 24 pointings to visual and audio-visual targets (Experiment 2), is sufficient to bring about AEs, as compared to the standard 92-pointings procedure. Finally, pointings to auditory targets cause AEs, although PA with a reduced number of pointings (24) to auditory targets brings about smaller AEs, as compared to the 92-pointings procedure (Experiment 3). Together, results from the three experiments extend to the auditory modality the sensorimotor plasticity underlying the typical AEs produced by PA to visual targets. Importantly, PA to auditory targets appears characterized by less accurate pointings and error correction, suggesting that the auditory component of the PA process may be less central to the building up of the AEs, than the sensorimotor pointing activity per se. These findings highlight both the effectiveness of a reduced number of pointings for bringing about AEs, and the possibility of inducing PA with auditory targets, which may be used as a compensatory route in patients with visual deficits. PMID:29213233

Modern Radiation Therapy for Nodal Non-Hodgkin Lymphoma—Target Definition and Dose Guidelines From the International Lymphoma Radiation Oncology Group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Illidge, Tim, E-mail: Tim.Illidge@ics.manchester.ac.uk; Specht, Lena; Yahalom, Joachim

2014-05-01

Radiation therapy (RT) is the most effective single modality for local control of non-Hodgkin lymphoma (NHL) and is an important component of therapy for many patients. Many of the historic concepts of dose and volume have recently been challenged by the advent of modern imaging and RT planning tools. The International Lymphoma Radiation Oncology Group (ILROG) has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the ILROG steering committee on the use of RT in NHL in the modern era. The roles of reduced volume and reduced doses aremore » addressed, integrating modern imaging with 3-dimensional planning and advanced techniques of RT delivery. In the modern era, in which combined-modality treatment with systemic therapy is appropriate, the previously applied extended-field and involved-field RT techniques that targeted nodal regions have now been replaced by limiting the RT to smaller volumes based solely on detectable nodal involvement at presentation. A new concept, involved-site RT, defines the clinical target volume. For indolent NHL, often treated with RT alone, larger fields should be considered. Newer treatment techniques, including intensity modulated RT, breath holding, image guided RT, and 4-dimensional imaging, should be implemented, and their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control.« less

Nanophotosensitizers toward advanced photodynamic therapy of Cancer.

PubMed

Lim, Chang-Keun; Heo, Jeongyun; Shin, Seunghoon; Jeong, Keunsoo; Seo, Young Hun; Jang, Woo-Dong; Park, Chong Rae; Park, Soo Young; Kim, Sehoon; Kwon, Ick Chan

2013-07-01

Photodynamic therapy (PDT) is a non-invasive treatment modality for selective destruction of cancer and other diseases and involves the colocalization of light, oxygen, and a photosensitizer (PS) to achieve photocytotoxicity. Although this therapeutic method has considerably improved the quality of life and life expectancy of cancer patients, further advances in selectivity and therapeutic efficacy are required to overcome numerous side effects related to classical PDT. The application of nanoscale photosensitizers (NPSs) comprising molecular PSs and nanocarriers with or without other biological/photophysical functions is a promising approach for improving PDT. In this review, we focus on four nanomedical approaches for advanced PDT: (1) nanocarriers for targeted delivery of PS, (2) introduction of active targeting moieties for disease-specific PDT, (3) stimulus-responsive NPSs for selective PDT, and (4) photophysical improvements in NPS for enhanced PDT efficacy. ► Conservation of normal tissues demands non-invasive therapeutic methods. ► PDT is a light-activated, non-invasive modality for selective destruction of cancers.► Success of PDT requires further advances to overcome the limitations of classical PDT. ►Nanophotosensitizers help improve target selectivity and therapeutic efficacy of PDT. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Acoustic Hemostasis and Hemorrhage Control in Combat Casualty Care

DTIC Science & Technology

2004-12-01

of Mississippi 1 Coliseum Drive University, MS 38677-1848 ABSTRACT High Intensity Focused Ultrasound ( HIFU ) is a new treatment modality that shows...Intensity Focused Ultrasound ( HIFU ) to this site to induce cauterization and to terminate/control the bleeding. We call this approach “Image-guided...during HIFU exposure to a porcine liver. Fig. 3. Illustration of the use of a hyperechoic region in the ultrasound image to provide HIFU targeting

Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

PubMed

Witcher, Mark R; Ellis, Thomas L

2012-01-01

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

Recent advances in radiation cancer therapy

NASA Astrophysics Data System (ADS)

Ma, C.-M. Charlie

2007-03-01

This paper presents the recent advances in radiation therapy techniques for the treatment of cancer. Significant improvement has been made in imaging techniques such as CT, MRI, MRS, PET, ultrasound, etc. that have brought marked advances in tumor target and critical structure delineation for treatment planning and patient setup and target localization for accurate dose delivery in radiation therapy of cancer. Recent developments of novel treatment modalities including intensity-modulated x-ray therapy (IMXT), energy- and intensity modulated electron therapy (MERT) and intensity modulated proton therapy (IMPT) together with the use of advanced image guidance have enabled precise dose delivery for dose escalation and hypofractionation studies that may result in better local control and quality of life. Particle acceleration using laser-induced plasmas has great potential for new cost-effective radiation sources that may have a great impact on the management of cancer using radiation therapy.

Visually augmented targeted combination light therapy for acne vulgaris: a case report.

PubMed

Yazdi, Alireza; Lyons, Colin-William; Roberts, Niamh

2017-10-31

Acne vulgaris is a common skin disease. Pharmacological modalities for treatment are proven to be efficacious but have limitations. Light therapy for acne vulgaris has shown promise in previous studies. This case report and its accompanying images show how a novel approach of visually augmented high fluence light therapy has been used to good effect. A 26-year-old Caucasian woman with acne vulgaris resistant to treatment with topical therapy underwent three sessions of combination potassium titanyl phosphate laser (532 nm)/neodymium-doped: yttrium aluminum garnet laser (1064 nm) light therapy with visually augmented narrow spot size and high fluence. A 73% reduction in total inflammatory lesions was evident 6 months after the initial treatment. This case report illustrates that there may be utility in this novel approach of narrow spot size, magnification-assisted, high fluence targeted combination laser therapy for inflammatory acne.

Advances in the treatment of portal hypertension in cirrhosis.

PubMed

Kimer, N; Wiese, S; Mo, S; Møller, S; Bendtsen, F

2016-08-01

Non-selective beta-blockers and handling of esophageal varices has been key elements in the treatment of portal hypertension in recent decades. Liver vein catheterization has been essential in diagnosis and monitoring of portal hypertension, but ongoing needs for noninvasive tools has led to research in areas of both biomarkers, and transient elastography, which displays promising results in discerning clinically significant portal hypertension. Novel research into the areas of hepatic stellate cell function and the dynamic components of portal hypertension has revealed promising areas of treatment modalities, targeting intestinal decontamination, angiogenesis, inflammation and oxidative stress. Future studies may reveal if these initiatives lead to developments of new drugs for treatment of portal hypertension.

Is Angiosome-Targeted Angioplasty Effective for Limb Salvage and Wound Healing in Diabetic Foot? : A Meta-Analysis.

PubMed

Chae, Kum Ju; Shin, Jin Yong

2016-01-01

Given that the efficacy of employing angiosome-targeted angioplasty in the treatment of diabetic foot remains controversial, this study was conducted to examine its efficacy. We performed a systematic literature review and meta-analysis using core databases, extracting the treatment modality of angiosome-targeted angioplasty as the predictor variable, and limb salvage, wound healing, and revision rate as the outcome variables. We used the Newcastle-Ottawa Scale to assess the study quality, along with the Cochrane Risk of Bias Tool. We evaluated publication bias using a funnel plot. The search strategy identified 518 publications. After screening these, we selected four articles for review. The meta-analysis revealed that overall limb salvage and wound healing rates were significantly higher (Odds ratio = 2.209, 3.290, p = 0.001, p<0.001) in patients who received angiosome-targeted angioplasty than in those who received nonangiosome-targeted angioplasty. The revision rate between the angiosome and nonangiosome groups was not significantly different (Odds ratio = 0.747, p = 0.314). Although a further randomized controlled trial is required for confirmation, angiosome-targeted angioplasty in diabetic foot was more effective than nonangiosome-targeted angioplasty with respect to wound healing and limb salvage.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larner, J.

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

Choice of modality with the use of high-performance membrane and evaluation for clinical effects.

PubMed

Masakane, Ikuto

2011-01-01

The golden target for dialysis therapy should be to guarantee longer survival and to give a higher quality of life without dialysis-related complications. In order to achieve this target, the choice of dialysis modality and membrane is essential but we have not yet established what the best choice for a dialysis modality and membrane are. Generally, we choose a dialysis modality for better solute removal and better biocompatibility. In this issue we would like to propose that the patients' preference for dialysis therapy is a useful parameter in prescribing the dialysis modality. In our recent experience, chronic dialysis patients have had preferences on a dialysis modality and membrane, those being PMMA, EVAL, AN-69 and pre-dilution online HDF. These modalities could relieve them of uncomfortable dialysis-related symptoms such as insomnia, itchiness, irritability, and so on. Other characteristics of these modalities are of a nutritional advantage, a broad removal pattern of uremic toxins including low-molecular-weight protein and protein-bound uremic toxins, and good biocompatibility free from chemical components of dialysis membrane. In conclusion, patients' symptoms could be a useful parameter to choose a dialysis modality and membrane. Copyright © 2011 S. Karger AG, Basel.

Management of skeletal metastases: An orthopaedic surgeon's guide

PubMed Central

Agarwal, Manish G; Nayak, Prakash

2015-01-01

Skeletal metastasis is a common cause of severe morbidity, reduction in quality of life (QOL) and often early mortality. Its prevalence is rising due to a higher rate of diagnosis, better systemic treatment, longer lives with the disease and higher disease burden rate. As people with cancer live longer and with rising sensitivity of body imaging and surveillance, the incidence of pathological fracture, metastatic epidural cord compression is rising and constitutes a challenge for the orthopedic surgeon to maintain their QOL. Metastatic disease is no longer a death sentence condemning patients to “terminal care.” In the era of multidisciplinary care and effective systemic targeted and nontargeted therapy, patient expectations of QOL, even during palliative end of care period is high. We lay emphasis on proving the diagnosis of metastasis by biopsy and histopathology and discuss imaging modalities to help estimate fracture risk and map disease extent. This article discusses at length the evidence and decision-making process of various modalities to treat skeletal metastasis. The modalities range from radiation including image-guided, stereotactic and whole body radiation, systemic targeted or hormonal therapy, spinal decompression with or without stabilization, extended curettage with stabilization, resection in select cases with megaprosthetic or biological reconstruction, percutaneous procedures using radio frequency ablation, cementoplasties and discusses the role of emerging modalities like high frequency ultrasound-guided ablation, cryotherapy and whole body radionuclide therapy. The focus lies on the role of multidisciplinary care, which considers complex decisions on patient centric prognosis, comorbidities, cost, feasibility and expectations in order to maximize outcomes on QOL issues. PMID:25593359

A passive acoustic device for real-time monitoring of the efficacy of shockwave lithotripsy treatment.

PubMed

Leighton, T G; Fedele, F; Coleman, A J; McCarthy, C; Ryves, S; Hurrell, A M; De Stefano, A; White, P R

2008-10-01

Extracorporeal shockwave lithotripsy (ESWL) is the preferred modality for the treatment of renal and ureteric stone disease. Currently X-ray or ultrasound B-scan imaging are used to locate the stone and to check that it remains targeted at the focus of the lithotripter during treatment. Neither imaging modality is particularly effective in allowing the efficacy of treatment to be judged during the treatment session. A new device is described that, when placed on the patient's skin, can passively monitor the acoustic signals that propagate through the body after each lithotripter shock, and which can provide useful information on the effectiveness of targeting. These acoustic time histories are analyzed in real time to extract the two main characteristic peak amplitudes (m(1) and m(2)) and the time between these peaks (t(c)). A set of rules based on the acoustic parameters was developed during a clinical study in which a complete set of acoustic and clinical data was obtained for 30 of the 118 subjects recruited. The rules, which complied with earlier computational fluid dynamics (CFD) modeling and in vitro tests, allow each shock to be classified as "effective" or "ineffective." These clinically-derived rules were then applied in a second clinical study in which complete datasets were obtained for 49 of the 85 subjects recruited. This second clinical study demonstrated almost perfect agreement (kappa = 0.94) between the number of successful treatments, defined as >50% fragmentation as determined by X-ray at the follow-up appointment, and a device-derived global treatment score, TS(0), a figure derived from the total number of effective shocks in any treatment. The acoustic system is shown to provide a test of the success of the treatment that has a sensitivity of 91.7% and a specificity of 100%. In addition to the predictive capability, the device provides valuable real-time feedback to the lithotripter operator by indicating the effectiveness of each shock, plus an indication TS(t) of the cumulative effectiveness of the shocks given so far in any treatment, and trends in key parameters. This feedback would allow targeting adjustments to be made during treatment. An example is given of its application to mistargeting because of respiration. tgl@soton.ac.uk

A modal radar cross section of thin-wire targets via the singularity expansion method

NASA Technical Reports Server (NTRS)

Richards, M. A.; Shumpert, T. H.; Riggs, L. S.

1992-01-01

A modal radar cross section (RCS) of arbitrary wire scatterers is constructed in terms of SEM parameters. Numerical results are presented for both straight and L-shaped wire targets and are compared to computations performed in the frequency domain using the method of moments.

Approach to investigation and treatment of persistent symptoms following sport-related concussion: a systematic review.

PubMed

Makdissi, Michael; Schneider, Kathryn J; Feddermann-Demont, Nina; Guskiewicz, Kevin M; Hinds, Sidney; Leddy, John J; McCrea, Michael; Turner, Michael; Johnston, Karen M

2017-06-01

To conduct a systematic review of the literature regarding assessment and treatment modalities in patients with persistent symptoms following sport-related concussion (SRC). We searched Medline, Embase, SPORTSDiscus, PsycINFO, CINAHL, Cochrane library and ProQuest Dissertation & Theses Global electronic databases. Studies were included if they were original research, reported on SRC as the primary source of injury, included patients with persistent postconcussive symptoms (>10 days) and investigated the role of assessment or treatment modalities. Of 3225 articles identified in the preliminary search, 25 articles met the inclusion criteria. 11 articles were concerned with assessment and 14 articles with treatment of persistent symptoms following SRC. There were three randomised control trials and one quasi-experimental study. The remainder consisting of cross-sectional studies, historical cohorts and case series. 'Persistent symptoms' following SRC can be defined as clinical recovery that falls outside expected time frames (ie, >10-14 days in adults and >4 weeks in children). It does not reflect a single pathophysiological entity, but describes a constellation of non-specific post-traumatic symptoms that may be linked to coexisting and/or confounding pathologies. A detailed multimodal clinical assessment is required to identify specific primary and secondary processes, and treatment should target specific pathologies identified. There is preliminary evidence supporting the use of symptom-limited aerobic exercise, targeted physical therapy and a collaborative approach that includes cognitive behavioural therapy. Management of patients with persistent symptoms is challenging and should occur in a multidisciplinary collaborative setting, with healthcare providers with experience in SRC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of surgery, immunization, and laser immunotherapy on a non-immunogenic metastic tumor model

NASA Astrophysics Data System (ADS)

Chen, Wei R.; Huang, Zheng; Andrienko, Kirill; Stefanov, Stefan; Wolf, Roman F.; Liu, Hong

2006-08-01

Traditional local cancer treatment modalities include surgery and radiation, which has the immediate tumor response due to tumor removal or radiation induced cell death. However, such therapeutic approaches usually do not result in eradiation of tumors, particularly when treating metastatic tumors. In fact, local treatment of primary tumors may stimulate the growth and spread of remote metastasis. Commonly used systemic therapies include chemotherapy and immunotherapy, which target the dividing cells or the immune systems. However, in addition to the severe side effects, chemotherapy often suppresses the immune systems, hence lessening the host's ability to fight the disease. Immunotherapy, on the other hand, aims at educating and stimulating immune systems using either general immune enhancements or antigen-oriented specific immune stimulation. However, so far, the traditional immunotherapy has yielded only limited success in treating cancer patients. A different approach is needed. To combine the advantages of both local therapies for acute and targeted treatment responses and the systemic therapies for stimulation of the immune systems, laser immunotherapy was proposed to use selective photothermal therapy as the local treatment modality and the adjuvant-assisted immunotherapy for systemic control. Laser immunotherapy has show positive results in treating metastatic tumors. In this study, we conducted a comparative study using surgery, freeze-thaw immunization and laser immunotherapy in the treatment of metastatic rat mammary tumors. Our results showed that removal of the primary tumors was unsuccessful at changing the course of tumor progression. The tumor cell lysate immunization delayed the emergence of metastases but did not provide immunity against the tumor challenge. Laser immunotherapy, on the other hand, resulted in regression and eradication.

MO-DE-210-03: Ultrasound imaging is an attractive method for image guided radiation treatment (IGRT), by itself or to complement other imaging modalities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, K.

Ultrasound imaging is an attractive method for image guided radiation treatment (IGRT), by itself or to complement other imaging modalities. It is inexpensive, portable and provides good soft tissue contrast. For challenging soft tissue targets such as pancreatic cancer, ultrasound imaging can be used in combination with pre-treatment MRI and/or CT to transfer important anatomical features for target localization at time of treatment. The non-invasive and non-ionizing nature of ultrasound imaging is particularly powerful for intra-fraction localization and monitoring. Recognizing these advantages, efforts are being made to incorporate novel robotic approaches to position and manipulate the ultrasound probe during irradiation.more » These recent enabling developments hold potential to bring ultrasound imaging to a new level of IGRT applications. However, many challenges, not limited to image registration, robotic deployment, probe interference and image acquisition rate, need to be addressed to realize the full potential of IGRT with ultrasound imaging. Learning Objectives: Understand the benefits and limitations in using ultrasound to augment MRI and/or CT for motion monitoring during radiation therapy delivery. Understanding passive and active robotic approaches to implement ultrasound imaging for intra-fraction monitoring. Understand issues of probe interference with radiotherapy treatment. Understand the critical clinical workflow for effective and reproducible IGRT using ultrasound guidance. The work of X.L. is supported in part by Elekta; J.W. and K.D. is supported in part by a NIH grant R01 CA161613 and by Elekta; D.H. is support in part by a NIH grant R41 CA174089.« less

Tracking Organs Composed of One or Multiple Regions Using Geodesic Active Region Models

NASA Astrophysics Data System (ADS)

Martínez, A.; Jiménez, J. J.

In radiotherapy treatment it is very important to find out the target organs on the medical image sequence in order to determine and apply the proper dose. The techniques to achieve this goal can be classified into extrinsic and intrinsic. Intrinsic techniques only use image processing with medical images associated to the radiotherapy treatment, as we deal in this chapter. To accurately perform this organ tracking it is necessary to find out segmentation and tracking models that were able to be applied to several image modalities involved on a radiotherapy session (CT See Modality , MRI , etc.). The movements of the organs are mainly affected by two factors: breathing and involuntary movements associated with the internal organs or patient positioning. Among the several alternatives to track the organs of interest, a model based on geodesic active regions is proposed. This model has been tested over CT images from the pelvic, cardiac, and thoracic area. A new model for the segmentation of organs composed by more than one region is proposed.

Colorectal Cancer Screening: Stool DNA and Other Noninvasive Modalities.

PubMed

Bailey, James R; Aggarwal, Ashish; Imperiale, Thomas F

2016-03-01

Colorectal cancer screening dates to the discovery of precancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study.

Subliminal semantic priming in speech.

PubMed

Daltrozzo, Jérôme; Signoret, Carine; Tillmann, Barbara; Perrin, Fabien

2011-01-01

Numerous studies have reported subliminal repetition and semantic priming in the visual modality. We transferred this paradigm to the auditory modality. Prime awareness was manipulated by a reduction of sound intensity level. Uncategorized prime words (according to a post-test) were followed by semantically related, unrelated, or repeated target words (presented without intensity reduction) and participants performed a lexical decision task (LDT). Participants with slower reaction times in the LDT showed semantic priming (faster reaction times for semantically related compared to unrelated targets) and negative repetition priming (slower reaction times for repeated compared to semantically related targets). This is the first report of semantic priming in the auditory modality without conscious categorization of the prime.

Subliminal Semantic Priming in Speech

PubMed Central

Tillmann, Barbara; Perrin, Fabien

2011-01-01

Numerous studies have reported subliminal repetition and semantic priming in the visual modality. We transferred this paradigm to the auditory modality. Prime awareness was manipulated by a reduction of sound intensity level. Uncategorized prime words (according to a post-test) were followed by semantically related, unrelated, or repeated target words (presented without intensity reduction) and participants performed a lexical decision task (LDT). Participants with slower reaction times in the LDT showed semantic priming (faster reaction times for semantically related compared to unrelated targets) and negative repetition priming (slower reaction times for repeated compared to semantically related targets). This is the first report of semantic priming in the auditory modality without conscious categorization of the prime. PMID:21655277

Nanoparticle-enhanced synergistic HIFU ablation and transarterial chemoembolization for efficient cancer therapy

NASA Astrophysics Data System (ADS)

You, Yufeng; Wang, Zhigang; Ran, Haitao; Zheng, Yuanyi; Wang, Dong; Xu, Jinshun; Wang, Zhibiao; Chen, Yu; Li, Pan

2016-02-01

High-intensity focused ultrasound (HIFU) is being generally explored as a non-invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high-efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment.

TOPICAL REVIEW: A review of dosimetry studies on external-beam radiation treatment with respect to second cancer induction

NASA Astrophysics Data System (ADS)

Xu, X. George; Bednarz, Bryan; Paganetti, Harald

2008-07-01

It has been long known that patients treated with ionizing radiation carry a risk of developing a second cancer in their lifetimes. Factors contributing to the recently renewed concern about the second cancer include improved cancer survival rate, younger patient population as well as emerging treatment modalities such as intensity-modulated radiation treatment (IMRT) and proton therapy that can potentially elevate secondary exposures to healthy tissues distant from the target volume. In the past 30 years, external-beam treatment technologies have evolved significantly, and a large amount of data exist but appear to be difficult to comprehend and compare. This review article aims to provide readers with an understanding of the principles and methods related to scattered doses in radiation therapy by summarizing a large collection of dosimetry and clinical studies. Basic concepts and terminology are introduced at the beginning. That is followed by a comprehensive review of dosimetry studies for external-beam treatment modalities including classical radiation therapy, 3D-conformal x-ray therapy, intensity-modulated x-ray therapy (IMRT and tomotherapy) and proton therapy. Selected clinical data on second cancer induction among radiotherapy patients are also covered. Problems in past studies and controversial issues are discussed. The needs for future studies are presented at the end.

Technique for comprehensive head and neck irradiation using 3-dimensional conformal proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Mark W., E-mail: markmcdonaldmd@gmail.com; Indiana University Health Proton Therapy Center, Bloomington, IN; Walter, Alexander S.

2015-01-01

Owing to the technical and logistical complexities of matching photon and proton treatment modalities, we developed and implemented a technique of comprehensive head and neck radiation using 3-dimensional (3D) conformal proton therapy. A monoisocentric technique was used with a 30-cm snout. Cervical lymphatics were treated with 3 fields: a posterior-anterior field with a midline block and a right and a left posterior oblique field. The matchline of the 3 cervical nodal fields with the primary tumor site fields was staggered by 0.5 cm. Comparative intensity-modulated photon plans were later developed for 12 previously treated patients to provide equivalent target coverage,more » while matching or improving on the proton plans' sparing of organs at risk (OARs). Dosimetry to OARs was evaluated and compared by treatment modality. Comprehensive head and neck irradiation using proton therapy yielded treatment plans with significant dose avoidance of the oral cavity and midline neck structures. When compared with the generated intensity-modulated radiation therapy (IMRT) plans, the proton treatment plans yielded statistically significant reductions in the mean and integral radiation dose to the oral cavity, larynx, esophagus, and the maximally spared parotid gland. There was no significant difference in mean dose to the lesser-spared parotid gland by treatment modality or in mean or integral dose to the spared submandibular glands. A technique for cervical nodal irradiation using 3D conformal proton therapy with uniform scanning was developed and clinically implemented. Use of proton therapy for cervical nodal irradiation resulted in large volume of dose avoidance to the oral cavity and low dose exposure to midline structures of the larynx and the esophagus, with lower mean and integral dose to assessed OARs when compared with competing IMRT plans.« less

Neurostimulation as a promising epilepsy therapy.

PubMed

Lin, Yicong; Wang, Yuping

2017-12-01

The revolution in theory, swift technological developments, and invention of new devices have driven tremendous progress in neurostimulation as a third-line treatment for epilepsy. Over the past decades, neurostimulation took its place in the field of epilepsy as an advanced treatment technique and opened up a new world. Numerous animal studies have proven the physical efficacy of stimulation of the brain and peripheral nerves. Based on this optimistic fundamental research, new advanced techniques are being explored in clinical practice. Over the past century, drawing on the benefits brought about by vagus nerve stimulation for the treatment of epilepsy, various new neurostimulation modalities have been developed to control seizures. Clinical studies including case reports, case series, and clinical trials have been booming in the past several years. This article gives a comprehensive review of most of these clinical studies. In addition to highlighting the advantages of neurostimulation for the treatment of epilepsy, concerns with this modality and future development directions are also discussed. The biggest advantage of neurostimulation over pharmacological treatments for epilepsy is the modulation of the epilepsy network by delivering stimuli at a specific target or the "hub." Conversely, however, a lack of knowledge of epilepsy networks and the mechanisms of neurostimulation may hinder further development. Therefore, theoretical research on the mechanism of epileptogenesis and epilepsy networks is needed in the future. Within the multiple modalities of neuromodulation, the final choice should be made after full discussion with a multidisciplinary team at a presurgical conference. Furthermore, the establishment of a neurostimulation system with standardized parameters and rigorous guidelines is another important issue. To achieve this goal, a worldwide collaboration of epilepsy centers is also suggested in the future.

SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdollahi, H

Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment responsemore » in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.« less

Effectiveness of Psychotherapy in Personality Disorders Not Otherwise Specified: A Comparison of Different Treatment Modalities.

PubMed

Horn, Eva K; Bartak, Anna; Meerman, Anke M M A; Rossum, Bert V; Ziegler, Uli M; Thunnissen, Moniek; Soons, Mirjam; Andrea, Helene; Hamers, Elisabeth F M; Emmelkamp, Paul M G; Stijnen, Theo; Busschbach, Jan J V; Verheul, Roel

2015-01-01

Although personality disorder not otherwise specified (PDNOS) is highly prevalent and associated with a high burden of disease, only a few treatment studies in this patient group exist. This study is the first to investigate the effectiveness of different modalities of psychotherapy in patients with PDNOS, i.e., short-term (up to 6 months) and long-term (more than 6 months) outpatient, day hospital, and inpatient psychotherapy. A total of 205 patients with PDNOS were assigned to one of six treatment modalities. Effectiveness was assessed over 60 months after baseline. The primary outcome measure was symptom severity, and the secondary outcome measures included psychosocial functioning and quality of life. The study design was quasi-experimental, and the multiple propensity score was used to control for initial differences between treatment groups. All treatment modalities showed positive outcomes, especially in terms of improvements of symptom severity and social role functioning. At 12-month follow-up, after adjustment for initial differences between the treatment groups, short-term outpatient psychotherapy and short-term inpatient psychotherapy showed most improvement and generally outperformed the other modalities concerning symptom severity. At 60 months after baseline, effectiveness remained but observed differences between modalities mostly diminished. Patients with PDNOS benefit from psychotherapy both at short-term and long-term follow-up. Short-term outpatient psychotherapy and short-term inpatient psychotherapy seem to be superior to the other treatment modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly comparable effectiveness. The effectiveness of different modalities of psychotherapy in patients with PDNOS (i.e., short-term vs long-term; outpatient versus day hospital versus inpatient psychotherapy) has not yet been compared. Different modalities of psychotherapy are effective for patients with PDNOS, and positive effects remain after 5 years. In patients with PDNOS short-term (less than 6 months) outpatient psychotherapy and short-term inpatient psychotherapy seem to be superior to the four other treatment modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly comparable effectiveness. Copyright © 2014 John Wiley & Sons, Ltd.

Helium ions for radiotherapy? Physical and biological verifications of a novel treatment modality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krämer, Michael, E-mail: m.kraemer@gsi.de; Scifoni, Emanuele; Schuy, Christoph

Purpose: Modern facilities for actively scanned ion beam radiotherapy allow in principle the use of helium beams, which could present specific advantages, especially for pediatric tumors. In order to assess the potential use of these beams for radiotherapy, i.e., to create realistic treatment plans, the authors set up a dedicated {sup 4}He beam model, providing base data for their treatment planning system TRiP98, and they have reported that in this work together with its physical and biological validations. Methods: A semiempirical beam model for the physical depth dose deposition and the production of nuclear fragments was developed and introduced inmore » TRiP98. For the biological effect calculations the last version of the local effect model was used. The model predictions were experimentally verified at the HIT facility. The primary beam attenuation and the characteristics of secondary charged particles at various depth in water were investigated using {sup 4}He ion beams of 200 MeV/u. The nuclear charge of secondary fragments was identified using a ΔE/E telescope. 3D absorbed dose distributions were measured with pin point ionization chambers and the biological dosimetry experiments were realized irradiating a Chinese hamster ovary cells stack arranged in an extended target. Results: The few experimental data available on basic physical processes are reproduced by their beam model. The experimental verification of absorbed dose distributions in extended target volumes yields an overall agreement, with a slight underestimation of the lateral spread. Cell survival along a 4 cm extended target is reproduced with remarkable accuracy. Conclusions: The authors presented a simple simulation model for therapeutical {sup 4}He beams which they introduced in TRiP98, and which is validated experimentally by means of physical and biological dosimetries. Thus, it is now possible to perform detailed treatment planning studies with {sup 4}He beams, either exclusively or in combination with other ion modalities.« less

IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative Treatments and Therapeutic Modalities)

DTIC Science & Technology

2010-02-01

in t heir o ptimal g rowth media a nd h arvested an d l ysed t hen analyzed by Western bl otting f or t he expression of H sp90, Hsp27 , Hsp60...analyzed by western blotting for the expression of Hsp27 , 70 and 90. The same membrane was probed with actin as a control for protein loading

The genetic basis of new treatment modalities in melanoma.

PubMed

Kunz, Manfred

2015-01-01

In recent years, intracellular signal transduction via RAS-RAF-MEK-ERK has been successfully targeted in new treatment approaches for melanoma using small molecule inhibitors against activated BRAF (V600E mutation) and activated MEK1/2. Also mutated c-KIT has been identified as a promising target. Meanwhile, evidence has been provided that combinations between BRAF inhibitors and MEK1/2 inhibitors are more promising than single-agent treatments. Moreover, new treatment algorithms favor sequential treatment using BRAF inhibitors and newly developed immunotherapies targeting common T lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1). In depth molecular analyses have uncovered new mechanisms of treatment resistance and recurrence, which may impact on future treatment decisions. Moreover, next-generation sequencing data have shown that recurrent lesions harbor specific genetic aberrations. At the same time, high throughput sequencing studies of melanoma unraveled a series of new treatment candidates for future treatment approaches such as ERBB4, GRIN2A, GRM3, and RAC1. More recent bioinformatic technologies provided genetic evidence for extensive tumor heterogeneity and tumor clonality of solid tumors, which might also be of relevance for melanoma. However, these technologies have not yet been applied to this tumor. In this review, an overview on the genetic basis of current treatment of melanoma, treatment resistance and recurrences including new treatment perspectives based on recent high-throughput sequencing data is provided. Moreover, future aspects of individualized treatment based on each patient's individual mutational landscape are discussed.

Non-invasive detection of vulnerable coronary plaque

PubMed Central

Sharif, Faisal; Lohan, Derek G; Wijns, William

2011-01-01

Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes and sudden cardiac death. Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and non-invasive imaging techniques have shown the potential to identify these high-risk plaques. Non-invasive imaging with magnetic resonance imaging, computed tomography and positron emission tomography holds the potential to differentiate between low- and high-risk plaques. There have been significant technological advances in non-invasive imaging modalities, and the aim is to achieve a diagnostic sensitivity for these technologies similar to that of the invasive modalities. Molecular imaging with the use of novel targeted nanoparticles may help in detecting high-risk plaques that will ultimately cause acute myocardial infarction. Moreover, nanoparticle-based imaging may even provide non-invasive treatments for these plaques. However, at present none of these imaging modalities are able to detect vulnerable plaque nor have they been shown to definitively predict outcome. Further trials are needed to provide more information regarding the natural history of high-risk but non-flow-limiting plaque to establish patient specific targeted therapy and to refine plaque stabilizing strategies in the future. PMID:21860703

Thermoresponsive core-shell magnetic nanoparticles for combined modalities of cancer therapy.

PubMed

Purushotham, S; Chang, P E J; Rumpel, H; Kee, I H C; Ng, R T H; Chow, P K H; Tan, C K; Ramanujan, R V

2009-07-29

Thermoresponsive polymer-coated magnetic nanoparticles loaded with anti-cancer drugs are of considerable interest for novel multi-modal cancer therapies. Such nanoparticles can be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release. Gamma-Fe(2)O(3) iron oxide magnetic nanoparticles (MNP) with average sizes of 14, 19 and 43 nm were synthesized by high temperature decomposition. Composite magnetic nanoparticles (CNP) of 43 nm MNP coated with the thermoresponsive polymer poly-n-isopropylacrylamide (PNIPAM) were prepared by dispersion polymerization of n-isopropylacrylamide monomer in the presence of the MNP. In vitro drug release of doxorubicin-(dox) loaded dehydrated CNP at temperatures below and above the lower critical solution temperature of PNIPAM (34 degrees C) revealed a weak dependence of drug release on swelling behavior. The particles displayed Fickian diffusion release kinetics; the maximum dox release at 42 degrees C after 101 h was 41%. In vitro simultaneous hyperthermia and drug release of therapeutically relevant quantities of dox was achieved, 14.7% of loaded dox was released in 47 min at hyperthermia temperatures. In vivo magnetic targeting of dox-loaded CNP to hepatocellular carcinoma (HCC) in a buffalo rat model was studied by magnetic resonance imaging (MRI) and histology. In summary, the good in vitro and in vivo performance of the doxorubicin-loaded thermoresponsive polymer-coated magnetic nanoparticles suggests considerable promise for applications in multi-modal treatment of cancer.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Psychological factors in oral mucosal and orofacial pain conditions.

PubMed

Alrashdan, Mohammad S; Alkhader, Mustafa

2017-01-01

The psychological aspects of chronic pain conditions represent a key component of the pain experience, and orofacial pain conditions are not an exception. In this review, we highlight how psychological factors affect some common oral mucosal and orofacial pain conditions (namely, oral lichen planus, recurrent aphthous stomatitis, burning mouth syndrome, and temporomandibular disorders) with emphasis on the significance of supplementing classical biomedical treatment modalities with appropriate psychological counseling to improve treatment outcomes in targeted patients. A literature search restricted to reports with highest relevance to the selected mucosal and orofacial pain conditions was carried out to retrieve data.

Development of the "Treatment beliefs in knee and hip OsteoArthritis (TOA)" questionnaire.

PubMed

Selten, Ellen M H; Vriezekolk, Johanna E; Schers, Henk J; Nijhof, Marc W; van der Laan, Willemijn H; van der Meulen-Dilling, Roelien G; Geenen, Rinie; van den Ende, Cornelia H M

2017-09-19

Use of conservative treatment modalities in osteoarthritis (OA) is suboptimal, which appears to be partly due to patients' beliefs about treatments. The aim of this study was to develop a research instrument assessing patients' beliefs about various treatment modalities of hip and knee OA: the 'Treatment beliefs in OA (TOA) questionnaire'. The item pool that was retrieved from interviews with patients and healthcare providers comprised beliefs regarding five treatment modalities: physical activity, pain medication, physiotherapy, injections and arthroplasty. After an extensive selection procedure, a draft questionnaire with 200 items was constructed. Descriptive analyses and exploratory factor analyses with oblique rotation were conducted for each treatment modality separately to decide upon the final questionnaire. Internal consistency and test-retest reliability were determined. The final questionnaire comprised 60 items. It was completed by 351 patients with knee or hip OA. Each of the five treatment modalities yielded a two factor solution with 37% to 51% explained variance and high face validity. Factor I included 'positive treatment beliefs' and factor II 'negative treatment beliefs'. Internal consistency (Cronbach α's from 0.72 to 0.87) and test-retest reliability (i.e. intraclass correlation coefficient from 0.66-0.88; standard error of measurement from 0.06-0.11) were satisfactory to good. The TOA questionnaire is the first questionnaire assessing positive and negative treatment beliefs regarding five treatment modalities for knee and hip OA. The instrument will help to understand whether and to what extent treatment beliefs influence treatment choices.

Characterization and evaluation of ionizing and non-ionizing imaging systems used in state of the art image-guided radiation therapy techniques

NASA Astrophysics Data System (ADS)

Stanley, Dennis Nichols

With the growing incidence of cancer worldwide, the need for effective cancer treatment is paramount. Currently, radiation therapy exists as one of the few effective, non-invasive methods of reducing tumor size and has the capability for the elimination of localized tumors. Radiation therapy utilizes non-invasive external radiation to treat localized cancers but to be effective, physicians must be able to visualize and monitor the internal anatomy and target displacements. Image-Guided Radiation Therapy frequently utilizes planar and volumetric imaging during a course of radiation therapy to improve the precision and accuracy of the delivered treatment to the internal anatomy. Clinically, visualization of the internal anatomy allows physicians to refine the treatment to include as little healthy tissue as possible. This not only increases the effectiveness of treatment by damaging only the tumor but also increases the quality of life for the patient by decreasing the amount of healthy tissue damaged. Image-Guided Radiation Therapy is commonly used to treat tumors in areas of the body that are prone to movement, such as the lungs, liver, and prostate, as well as tumors located close to critical organs and tissues such as the tumors in the brain and spinal cord. Image-Guided Radiation Therapy can utilize both ionizing modalities, like x-ray based planar radiography and cone-beam CT, and nonionizing modalities like MRI, ultrasound and video-based optical scanning systems. Currently ionizing modalities are most commonly utilized for their ability to visualize and monitor internal anatomy but cause an increase to the total dose to the patient. Nonionizing imaging modalities allow frequent/continuous imaging without the increase in dose; however, they are just beginning to be clinically implemented in radiation oncology. With the growing prevalence and variety of Image-Guided Radiation Therapy imaging modalities the ability to evaluate the overall image quality, monitor the stability of the imaging systems and characterize each system are important to ensuring the consistency and effectiveness of the overall treatment. Image-Guided Radiation Therapy quality assurance allows a method of quantifying the accuracy and stability of the imaging systems. Understanding how the ionizing imaging systems operate and change over time allows for a more effective overall treatment and will be the focus of the first step of this project. In each of the first three aims, different ionizing imaging modalities will be evaluated for their temporal stability and a record of the determined tolerance level will be reported. The Second step of this project will be a characterization of the accuracy and performance of the new C-Rad CatalystHD a video-based, surface-imaging guided patient localization system. The catalyst will be analyzed for it accuracy of setup and patient positing, intra- and inter- fraction motion detection as well as its respiratory gating capabilities. The final step of this project will be to use the well-established accuracy of the XVI volumetric imaging system as a benchmark to assess the accuracy of the C-Rad CatalystHD system for use in pretreatment patient position verification for cranial stereotactic procedures. The treatment of brain lesions generally requires a very high degree of precision due to relatively small target sizes, close proximity to eloquent areas of the brain, and large, ablative doses being delivered. Stringent accuracy in imaging is needed to verify and monitor the correct spatial delivery of radiation throughout treatment. In order to investigate if the CatalystHD system is a capable imaging system for such deliveries, the system will need to be assessed and benchmarked against the XVI in a phantom geometry. By doing so, the currently unproven utility of the CatalystHD system for cranial stereotactic delivery may be established. (Abstract shortened by ProQuest.).

Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

PubMed Central

Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

2016-01-01

Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA.

PubMed

Costales, Matthew G; Rzuczek, Suzanne G; Disney, Matthew D

2016-06-01

Potential RNA targets for chemical probes and therapeutic modalities are pervasive in the transcriptome. Oligonucleotide-based therapeutics are commonly used to target RNA sequence. Small molecules are emerging as a modality to target RNA structures selectively, but their development is still in its infancy. In this work, we compare the activity of oligonucleotides and several classes of small molecules that target the non-coding r(CCUG) repeat expansion (r(CCUG)(exp)) that causes myotonic dystrophy type 2 (DM2), an incurable disease that is the second-most common cause of adult onset muscular dystrophy. Small molecule types investigated include monomers, dimers, and multivalent compounds synthesized on-site by using RNA-templated click chemistry. Oligonucleotides investigated include phosphorothioates that cleave their target and vivo-morpholinos that modulate target RNA activity via binding. We show that compounds assembled on-site that recognize structure have the highest potencies amongst small molecules and are similar in potency to a vivo-morpholino modified oligonucleotide that targets sequence. These studies are likely to impact the design of therapeutic modalities targeting other repeats expansions that cause fragile X syndrome and amyotrophic lateral sclerosis, for example. Copyright © 2016. Published by Elsevier Ltd.

Nano anti-cancer drugs: pros and cons and future perspectives.

PubMed

Ali, Imran

2011-02-01

For last one decade, scientists are working for developing nano anti-cancer drugs with claim of ideal ones due to their targeted chemotherapic nature. These drugs have many beneficial properties such as targeted drug delivery and gene therapy modalities with minimum side effects. This article describes pros and cons and future perspectives of nano anti-cancer drugs. Efforts have been made to address importance, special features, toxicities (general, blood identities, immune system and environmental) and future perspectives of nano anti-cancer drugs. It was concluded that nano anti-cancer drugs may be magic bullet drugs for cancer treatment leading to bright future of the whole world.

Novel immunotherapy and treatment modality for severe food allergies.

PubMed

Nagakura, Ken-Ichi; Sato, Sakura; Yanagida, Noriyuki; Ebisawa, Motohiro

2017-06-01

In recent years, many studies on oral immunotherapy (OIT) have been conducted; however, few have focused on severe food allergies. The purpose of this review was to assess the efficacy and safety of oral immunotherapies for patients with severe food allergy. We reviewed multiple immunotherapy reports published within a few years or reports focusing on severe food allergies. We also investigated recent studies on OIT and novel food allergy management. Immunotherapies targeting low-dose antigen exposure and oral food challenges using low-dose target volumes may be safer than conventional OIT. It is necessary to consider which immunotherapy regimen is appropriate based on allergy severity of the patient.

Structure-based receptor MIMICS targeted against bacterial superantigen toxins

DOEpatents

Gupta, Goutam [Santa Fe, NM; Hong-Geller, Elizabeth [Los Alamos, NM; Shiflett, Patrick R [Los Alamos, NM; Lehnert, Nancy M [Albuquerque, NM

2009-08-18

The invention provides therapeutic compositions useful in the treatment of bacterial superantigen mediated conditions, such as Toxic Shock Syndrome. The compositions comprise genetically engineered bifunctional polypeptides containing a specific T-cell receptor binding domain and a specific MHC class II receptor binding domain, each targeting non-overlapping epitopes on a superantigen molecule against which they are designed. The anti-superantigen "receptor mimetics" or "chimeras" are rationally designed to recreate the modality of superantigen binding directly to both the TCR and the MHC-II receptor, and are capable of acting as decoys for superantigen binding, effectively out-competing the host T-cell and MHC-II receptors, the natural host receptors.

Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses.

PubMed

Ferraro, Bernadette; Cisper, Neil J; Talbott, Kendra T; Philipson-Weiner, Lindsey; Lucke, Colleen E; Khan, Amir S; Sardesai, Niranjan Y; Weiner, David B

2011-01-01

Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa.

A Multimodal Communication Program for Aphasia during Inpatient Rehabilitation: A Case Study

PubMed Central

Wallace, Sarah E.; Purdy, Mary; Skidmore, Elizabeth

2014-01-01

BACKGROUND Communication is essential for successful rehabilitation, yet few aphasia treatments have been investigated during the acute stroke phase. Alternative modality use including gesturing, writing, or drawing has been shown to increase communicative effectiveness in people with chronic aphasia. Instruction in alternative modality use during acute stroke may increase patient communication and participation, therefore resulting in fewer adverse situations and improved rehabilitation outcomes. OBJECTIVE The study purpose was to explore a multimodal communication program for aphasia (MCPA) implemented during acute stroke rehabilitation. MCPA aims to improve communication modality production, and to facilitate switching among modalities to resolve communication breakdowns. METHODS Two adults with severe aphasia completed MCPA beginning at 2 and 3 weeks post onset a single left-hemisphere stroke. Probes completed during each session allowed for evaluation of modality production and modality switching accuracy. RESULTS Participants completed MCPA (10 and 14 treatment sessions respectively) and their performance on probes suggested increased accuracy in the production of various alternate communication modalities. However, increased switching to an alternate modality was noted for only one participant. CONCLUSIONS Further investigation of multimodal treatment during inpatient rehabilitation is warranted. In particular, comparisons between multimodal and standard treatments would help determine appropriate interventions for this setting. PMID:25227547

Combining transrectal ultrasound and CT for image-guided adaptive brachytherapy of cervical cancer: Proof of concept.

PubMed

Nesvacil, Nicole; Schmid, Maximilian P; Pötter, Richard; Kronreif, Gernot; Kirisits, Christian

To investigate the feasibility of a treatment planning workflow for three-dimensional image-guided cervix cancer brachytherapy, combining volumetric transrectal ultrasound (TRUS) for target definition with CT for dose optimization to organs at risk (OARs), for settings with no access to MRI. A workflow for TRUS/CT-based volumetric treatment planning was developed, based on a customized system including ultrasound probe, stepper unit, and software for image volume acquisition. A full TRUS/CT-based workflow was simulated in a clinical case and compared with MR- or CT-only delineation. High-risk clinical target volume was delineated on TRUS, and OARs were delineated on CT. Manually defined tandem/ring applicator positions on TRUS and CT were used as a reference for rigid registration of the image volumes. Treatment plan optimization for TRUS target and CT organ volumes was performed and compared to MRI and CT target contours. TRUS/CT-based contouring, applicator reconstruction, image fusion, and treatment planning were feasible, and the full workflow could be successfully demonstrated. The TRUS/CT plan fulfilled all clinical planning aims. Dose-volume histogram evaluation of the TRUS/CT-optimized plan (high-risk clinical target volume D 90 , OARs D 2cm³ for) on different image modalities showed good agreement between dose values reported for TRUS/CT and MRI-only reference contours and large deviations for CT-only target parameters. A TRUS/CT-based workflow for full three-dimensional image-guided cervix brachytherapy treatment planning seems feasible and may be clinically comparable to MRI-based treatment planning. Further development to solve challenges with applicator definition in the TRUS volume is required before systematic applicability of this workflow. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Attentional Shifts between Audition and Vision in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Occelli, Valeria; Esposito, Gianluca; Venuti, Paola; Arduino, Giuseppe Maurizio; Zampini, Massimiliano

2013-01-01

Previous evidence on neurotypical adults shows that the presentation of a stimulus allocates the attention to its modality, resulting in faster responses to a subsequent target presented in the same (vs. different) modality. People with Autism Spectrum Disorders (ASDs) often fail to detect a (visual or auditory) target in a stream of stimuli after…

Automatic selective attention as a function of sensory modality in aging.

PubMed

Guerreiro, Maria J S; Adam, Jos J; Van Gerven, Pascal W M

2012-03-01

It was recently hypothesized that age-related differences in selective attention depend on sensory modality (Guerreiro, M. J. S., Murphy, D. R., & Van Gerven, P. W. M. (2010). The role of sensory modality in age-related distraction: A critical review and a renewed view. Psychological Bulletin, 136, 975-1022. doi:10.1037/a0020731). So far, this hypothesis has not been tested in automatic selective attention. The current study addressed this issue by investigating age-related differences in automatic spatial cueing effects (i.e., facilitation and inhibition of return [IOR]) across sensory modalities. Thirty younger (mean age = 22.4 years) and 25 older adults (mean age = 68.8 years) performed 4 left-right target localization tasks, involving all combinations of visual and auditory cues and targets. We used stimulus onset asynchronies (SOAs) of 100, 500, 1,000, and 1,500 ms between cue and target. The results showed facilitation (shorter reaction times with valid relative to invalid cues at shorter SOAs) in the unimodal auditory and in both cross-modal tasks but not in the unimodal visual task. In contrast, there was IOR (longer reaction times with valid relative to invalid cues at longer SOAs) in both unimodal tasks but not in either of the cross-modal tasks. Most important, these spatial cueing effects were independent of age. The results suggest that the modality hypothesis of age-related differences in selective attention does not extend into the realm of automatic selective attention.

Behold the voice of wrath: cross-modal modulation of visual attention by anger prosody.

PubMed

Brosch, Tobias; Grandjean, Didier; Sander, David; Scherer, Klaus R

2008-03-01

Emotionally relevant stimuli are prioritized in human information processing. It has repeatedly been shown that selective spatial attention is modulated by the emotional content of a stimulus. Until now, studies investigating this phenomenon have only examined within-modality effects, most frequently using pictures of emotional stimuli to modulate visual attention. In this study, we used simultaneously presented utterances with emotional and neutral prosody as cues for a visually presented target in a cross-modal dot probe task. Response times towards targets were faster when they appeared at the location of the source of the emotional prosody. Our results show for the first time a cross-modal attentional modulation of visual attention by auditory affective prosody.

A New Era of Image Guidance with Magnetic Resonance-guided Radiation Therapy for Abdominal and Thoracic Malignancies

PubMed Central

Paliwal, Bhudatt; Hill, Patrick; Bayouth, John E; Geurts, Mark W; Baschnagel, Andrew M; Bradley, Kristin A; Harari, Paul M; Rosenberg, Stephen; Brower, Jeffrey V; Wojcieszynski, Andrzej P; Hullett, Craig; Bayliss, R A; Labby, Zacariah E; Bassetti, Michael F

2018-01-01

Magnetic resonance-guided radiation therapy (MRgRT) offers advantages for image guidance for radiotherapy treatments as compared to conventional computed tomography (CT)-based modalities. The superior soft tissue contrast of magnetic resonance (MR) enables an improved visualization of the gross tumor and adjacent normal tissues in the treatment of abdominal and thoracic malignancies. Online adaptive capabilities, coupled with advanced motion management of real-time tracking of the tumor, directly allow for high-precision inter-/intrafraction localization. The primary aim of this case series is to describe MR-based interventions for localizing targets not well-visualized with conventional image-guided technologies. The abdominal and thoracic sites of the lung, kidney, liver, and gastric targets are described to illustrate the technological advancement of MR-guidance in radiotherapy. PMID:29872602

Noncirrhotic portal hypertension.

PubMed

Da, Ben L; Koh, Christopher; Heller, Theo

2018-05-01

Noncirrhotic portal hypertension represents a heterogeneous group of liver disorders that is characterized by portal hypertension in the absence of cirrhosis. The purpose of this review is to serve as a guide on how to approach a patient with noncirrhotic portal hypertension with a focus on recent developments. Recent studies pertaining to noncirrhotic portal hypertension have investigated aetiological causes, mechanisms of disease, noninvasive diagnostic modalities, clinical characteristics in the paediatric population and novel treatment targets. Noncirrhotic portal hypertension is an underappreciated clinical entity that can be difficult to diagnosis without a healthy suspicion. Diagnosis then relies on a comprehensive understanding of the causes and clinical manifestations of this disease, as well as a careful interpretation of the liver biopsy. Noninvasive approaches to diagnosis may play a significant role moving forward in this disease. Treatment in NCPH remains largely targeted at the individual sequalae of portal hypertension.

Improving Atrial Fibrillation Therapy: Is There a Gene for That?

PubMed Central

Hucker, William J.; Hanley, Alan; Ellinor, Patrick T.

2017-01-01

Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment. In this review, we will summarize the available published data on gene therapy and discuss the challenges, opportunities, and limitations of this approach. PMID:28427583

Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation.

PubMed

Audehm, Stefan; Krackhardt, Angela M

2017-01-01

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a treatment option for a diversity of advanced hematopoietic malignancies providing hope for long-term responses especially due to immunogenic effects associated with the treatment modality. Despite respectable progress in the field, relapses and/or opportunistic infections are major reasons for the high treatment-related mortality. However, a number of novel immunotherapeutic approaches using defined cell populations have been developed to directly target residual malignant cells as well as defined infectious diseases. We here provide an overview of current adoptive cellular immunotherapies in the context of allo-HSCT and close with an outlook on new directions within the field. © 2017 S. Karger GmbH, Freiburg.

Cancer Nanotechnology: Recent Trends and Developments in Strategies for Targeting Cancer Cells to Improve Cancer Imaging and Treatment.

PubMed

Xu, Jingyao; Zhou, Xiaoling; Li, Yifei; Tian, Yudan

2017-01-01

Nanotechnology is a multidisciplinary field, which have the potential to cover applications in many subjects such as biology, chemistry and physics. The combined efforts of these subjects can lead to the successful engineering of nanodevices and nanovectors for targeted delivery and sensing/detection of cancer cells/tissues. The modulation of nanomaterials at surface and bulk level further adds value to this technology and develop strategies for early detection of precancerous and malignant cells from biological fluids. Furthermore, the novel nanotechnology-based imaging modalities have the prospects to offer non-invasive cancer imaging and treatment response study in real-time. This review covers the advantages of nanotechnology, which have been exploited for effective and targeted delivery of anti-cancer agents. Moreover, the initiatives taken by National Cancer Laboratory, USA to improve the clinical success of nanomedicines and nanovectors have also been comprehensively summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

PIRATE: pediatric imaging response assessment and targeting environment

NASA Astrophysics Data System (ADS)

Glenn, Russell; Zhang, Yong; Krasin, Matthew; Hua, Chiaho

2010-02-01

By combining the strengths of various imaging modalities, the multimodality imaging approach has potential to improve tumor staging, delineation of tumor boundaries, chemo-radiotherapy regime design, and treatment response assessment in cancer management. To address the urgent needs for efficient tools to analyze large-scale clinical trial data, we have developed an integrated multimodality, functional and anatomical imaging analysis software package for target definition and therapy response assessment in pediatric radiotherapy (RT) patients. Our software provides quantitative tools for automated image segmentation, region-of-interest (ROI) histogram analysis, spatial volume-of-interest (VOI) analysis, and voxel-wise correlation across modalities. To demonstrate the clinical applicability of this software, histogram analyses were performed on baseline and follow-up 18F-fluorodeoxyglucose (18F-FDG) PET images of nine patients with rhabdomyosarcoma enrolled in an institutional clinical trial at St. Jude Children's Research Hospital. In addition, we combined 18F-FDG PET, dynamic-contrast-enhanced (DCE) MR, and anatomical MR data to visualize the heterogeneity in tumor pathophysiology with the ultimate goal of adaptive targeting of regions with high tumor burden. Our software is able to simultaneously analyze multimodality images across multiple time points, which could greatly speed up the analysis of large-scale clinical trial data and validation of potential imaging biomarkers.

Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Noa, Kate; Wileyto, E. Paul

Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to comparemore » plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation. Using the IMRT or the SFUD plans instead of the 3-D conformal plan may improve both bowel and rectal toxicity.« less

Recent advances in aptamer-armed multimodal theranostic nanosystems for imaging and targeted therapy of cancer.

PubMed

Vandghanooni, Somayeh; Eskandani, Morteza; Barar, Jaleh; Omidi, Yadollah

2018-05-30

The side effects of chemotherapeutics during the course of cancer treatment limit their clinical outcomes. The most important mission of the modern cancer therapy modalities is the delivery of anticancer drugs specifically to the target cells/tissue in order to avoid/reduce any inadvertent non-specific impacts on the healthy normal cells. Nanocarriers decorated with a designated targeting ligand such as aptamers (Aps) and antibodies (Abs) are able to deliver cargo molecules to the target cells/tissue without affecting other neighboring cells, resulting in an improved treatment of cancer. For targeted therapy of cancer, different ligands (e.g., protein, peptide, Abs, Aps and small molecules) have widely been used in the development of different targeting drug delivery systems (DDSs). Of these homing agents, nucleic acid Aps show unique targeting potential with high binding affinity to a variety of biological targets (e.g., genes, peptides, proteins, and even cells and organs). Aps have widely been used as the targeting agent, in large part due to their unique 3D structure, simplicity in synthesis and functionalization, high chemical flexibility, low immunogenicity and toxicity, and cell/tissue penetration capability in some cases. Here, in this review, we provide important insights on Ap-decorated multimodal nanosystems (NSs) and discuss their applications in targeted therapy and imaging of cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Selective Attention and Sensory Modality in Aging: Curses and Blessings.

PubMed

Van Gerven, Pascal W M; Guerreiro, Maria J S

2016-01-01

The notion that selective attention is compromised in older adults as a result of impaired inhibitory control is well established. Yet it is primarily based on empirical findings covering the visual modality. Auditory and especially, cross-modal selective attention are remarkably underexposed in the literature on aging. In the past 5 years, we have attempted to fill these voids by investigating performance of younger and older adults on equivalent tasks covering all four combinations of visual or auditory target, and visual or auditory distractor information. In doing so, we have demonstrated that older adults are especially impaired in auditory selective attention with visual distraction. This pattern of results was not mirrored by the results from our psychophysiological studies, however, in which both enhancement of target processing and suppression of distractor processing appeared to be age equivalent. We currently conclude that: (1) age-related differences of selective attention are modality dependent; (2) age-related differences of selective attention are limited; and (3) it remains an open question whether modality-specific age differences in selective attention are due to impaired distractor inhibition, impaired target enhancement, or both. These conclusions put the longstanding inhibitory deficit hypothesis of aging in a new perspective.

Unconscious Cross-Modal Priming of Auditory Sound Localization by Visual Words

ERIC Educational Resources Information Center

Ansorge, Ulrich; Khalid, Shah; Laback, Bernhard

2016-01-01

Little is known about the cross-modal integration of unconscious and conscious information. In the current study, we therefore tested whether the spatial meaning of an unconscious visual word, such as "up", influences the perceived location of a subsequently presented auditory target. Although cross-modal integration of unconscious…

Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma.

PubMed

Song, Do Seon; Nam, Soon Woo; Bae, Si Hyun; Kim, Jin Dong; Jang, Jeong Won; Song, Myeong Jun; Lee, Sung Won; Kim, Hee Yeon; Lee, Young Joon; Chun, Ho Jong; You, Young Kyoung; Choi, Jong Young; Yoon, Seung Kew

2015-02-28

To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC). A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively. In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P<0.001) and objective tumor response (P=0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P=0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P<0.001). Multivariate analysis identified tumor stage (P<0.001) and tumor type (P=0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P<0.001), surgical treatment (P=0.009), and multi-modal treatment (P=0.002) were identified as independent post-treatment prognostic factors. TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC.

Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma

PubMed Central

Song, Do Seon; Nam, Soon Woo; Bae, Si Hyun; Kim, Jin Dong; Jang, Jeong Won; Song, Myeong Jun; Lee, Sung Won; Kim, Hee Yeon; Lee, Young Joon; Chun, Ho Jong; You, Young Kyoung; Choi, Jong Young; Yoon, Seung Kew

2015-01-01

AIM: To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC). METHODS: A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively. RESULTS: In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P < 0.001) and objective tumor response (P = 0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P = 0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P < 0.001). Multivariate analysis identified tumor stage (P < 0.001) and tumor type (P = 0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P < 0.001), surgical treatment (P = 0.009), and multi-modal treatment (P = 0.002) were identified as independent post-treatment prognostic factors. CONCLUSION: TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC. PMID:25741147

Best Practices in Cancer Nanotechnology – Perspective from NCI Nanotechnology Alliance

PubMed Central

Zamboni, William C.; Torchilin, Vladimir; Patri, Anil; Hrkach, Jeff; Stern, Stephen; Lee, Robert; Nel, Andre; Panaro, Nicholas J.; Grodzinski, Piotr

2014-01-01

Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics. PMID:22669131

Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles

PubMed Central

Spyratou, Ellas; Makropoulou, Mersini; Sihver, Lembit

2017-01-01

Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment. PMID:29257070

Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop.

PubMed

Bikson, Marom; Brunoni, Andre R; Charvet, Leigh E; Clark, Vincent P; Cohen, Leonardo G; Deng, Zhi-De; Dmochowski, Jacek; Edwards, Dylan J; Frohlich, Flavio; Kappenman, Emily S; Lim, Kelvin O; Loo, Colleen; Mantovani, Antonio; McMullen, David P; Parra, Lucas C; Pearson, Michele; Richardson, Jessica D; Rumsey, Judith M; Sehatpour, Pejman; Sommers, David; Unal, Gozde; Wassermann, Eric M; Woods, Adam J; Lisanby, Sarah H

Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders. Published by Elsevier Inc.

Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop

PubMed Central

Bikson, Marom; Brunoni, Andre R.; Charvet, Leigh E.; Clark, Vincent P.; Cohen, Leonardo G.; Deng, Zhi-De; Dmochowski, Jacek; Edwards, Dylan J.; Frohlich, Flavio; Kappenman, Emily S.; Lim, Kelvin O.; Loo, Colleen; Mantovani, Antonio; McMullen, David P.; Parra, Lucas C.; Pearson, Michele; Richardson, Jessica D.; Rumsey, Judith M.; Sehatpour, Pejman; Sommers, David; Unal, Gozde; Wassermann, Eric M.; Woods, Adam J.; Lisanby, Sarah H.

2018-01-01

Background Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. Objective This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. Methods The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. Results Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. Conclusions These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders. PMID:29398575

Picosecond 532-nm neodymium-doped yttrium aluminum garnet laser-a promising modality for the management of verrucous epidermal nevi.

PubMed

Levi, Assi; Amitai, Dan Ben; Mimouni, Daniel; Leshem, Yael A; Arzi, Ofir; Lapidoth, Moshe

2018-04-01

The verrucous epidermal nevus (VEN) is the most common type of epidermal nevi. As lesions can be disfiguring, treatment is often sought. Many therapeutic approaches have been reported, with variable efficacy and safety. Picosecond (PS) lasers are novel laser devices designated to target small chromophores. A side effect of these lasers is blistering due to epidermal-dermal separation. We aimed to harness this side effect of the PS lasers to treat patients with VEN. The purpose of this study was to report our experience treating VEN using a PS 532-nm laser. We present a retrospective case series of six patients with large VEN who were treated using a PS 532-nm laser (2-6 treatments, 8-10 weeks apart). Response in clinical photographs was assessed by two independent dermatologists and graded on a scale of 0 (exacerbation) to 4 (76-100% improvement). Patient satisfaction was recorded on a scale of 1-5. All patients demonstrated significant improvement. Average improvement was 3.7 on the quartile scale of improvement. Patient satisfaction rate averaged 4.7. The PS 532-nm laser is a promising novel modality for the treatment of large VEN.

TU-FG-201-03: Automatic Pre-Delivery Verification Using Statistical Analysis of Consistencies in Treatment Plan Parameters by the Treatment Site and Modality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, S; Wu, Y; Chang, X

Purpose: A novel computer software system, namely APDV (Automatic Pre-Delivery Verification), has been developed for verifying patient treatment plan parameters right prior to treatment deliveries in order to automatically detect and prevent catastrophic errors. Methods: APDV is designed to continuously monitor new DICOM plan files on the TMS computer at the treatment console. When new plans to be delivered are detected, APDV checks the consistencies of plan parameters and high-level plan statistics using underlying rules and statistical properties based on given treatment site, technique and modality. These rules were quantitatively derived by retrospectively analyzing all the EBRT treatment plans ofmore » the past 8 years at authors’ institution. Therapists and physicists will be notified with a warning message displayed on the TMS computer if any critical errors are detected, and check results, confirmation, together with dismissal actions will be saved into database for further review. Results: APDV was implemented as a stand-alone program using C# to ensure required real time performance. Mean values and standard deviations were quantitatively derived for various plan parameters including MLC usage, MU/cGy radio, beam SSD, beam weighting, and the beam gantry angles (only for lateral targets) per treatment site, technique and modality. 2D-based rules of combined MU/cGy ratio and averaged SSD values were also derived using joint probabilities of confidence error ellipses. The statistics of these major treatment plan parameters quantitatively evaluate the consistency of any treatment plans which facilitates automatic APDV checking procedures. Conclusion: APDV could be useful in detecting and preventing catastrophic errors immediately before treatment deliveries. Future plan including automatic patient identify and patient setup checks after patient daily images are acquired by the machine and become available on the TMS computer. This project is supported by the Agency for Healthcare Research and Quality (AHRQ) under award 1R01HS0222888. The senior author received research grants from ViewRay Inc. and Varian Medical System.« less

MO-E-BRB-03: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salter, B.

2016-06-15

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

MO-E-BRB-01: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benedict, S.

2016-06-15

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

MO-E-BRB-00: PANEL DISCUSSION: SBRT/SRS Case Studies - Lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

Alterations to multisensory and unisensory integration by stimulus competition

PubMed Central

Rowland, Benjamin A.; Stanford, Terrence R.; Stein, Barry E.

2011-01-01

In environments containing sensory events at competing locations, selecting a target for orienting requires prioritization of stimulus values. Although the superior colliculus (SC) is causally linked to the stimulus selection process, the manner in which SC multisensory integration operates in a competitive stimulus environment is unknown. Here we examined how the activity of visual-auditory SC neurons is affected by placement of a competing target in the opposite hemifield, a stimulus configuration that would, in principle, promote interhemispheric competition for access to downstream motor circuitry. Competitive interactions between the targets were evident in how they altered unisensory and multisensory responses of individual neurons. Responses elicited by a cross-modal stimulus (multisensory responses) proved to be substantially more resistant to competitor-induced depression than were unisensory responses (evoked by the component modality-specific stimuli). Similarly, when a cross-modal stimulus served as the competitor, it exerted considerably more depression than did its individual component stimuli, in some cases producing more depression than predicted by their linear sum. These findings suggest that multisensory integration can help resolve competition among multiple targets by enhancing orientation to the location of cross-modal events while simultaneously suppressing orientation to events at alternate locations. PMID:21957224

Alterations to multisensory and unisensory integration by stimulus competition.

PubMed

Pluta, Scott R; Rowland, Benjamin A; Stanford, Terrence R; Stein, Barry E

2011-12-01

In environments containing sensory events at competing locations, selecting a target for orienting requires prioritization of stimulus values. Although the superior colliculus (SC) is causally linked to the stimulus selection process, the manner in which SC multisensory integration operates in a competitive stimulus environment is unknown. Here we examined how the activity of visual-auditory SC neurons is affected by placement of a competing target in the opposite hemifield, a stimulus configuration that would, in principle, promote interhemispheric competition for access to downstream motor circuitry. Competitive interactions between the targets were evident in how they altered unisensory and multisensory responses of individual neurons. Responses elicited by a cross-modal stimulus (multisensory responses) proved to be substantially more resistant to competitor-induced depression than were unisensory responses (evoked by the component modality-specific stimuli). Similarly, when a cross-modal stimulus served as the competitor, it exerted considerably more depression than did its individual component stimuli, in some cases producing more depression than predicted by their linear sum. These findings suggest that multisensory integration can help resolve competition among multiple targets by enhancing orientation to the location of cross-modal events while simultaneously suppressing orientation to events at alternate locations.

Randomized phase II--study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer--PARC: study protocol [ISRCTN56652283].

PubMed

Krempien, R; Muenter, M W; Huber, P E; Nill, S; Friess, H; Timke, C; Didinger, B; Buechler, P; Heeger, S; Herfarth, K K; Abdollahi, A; Buchler, M W; Debus, J

2005-10-11

Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR. The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrollment. The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life.

Management of localized and locally advanced renal tumors. A contemporary review of current treatment options.

PubMed

Brookman-May, S; Langenhuijsen, J F; Volpe, A; Minervini, A; Joniau, S; Salagierski, M; Roscigno, M; Akdogan, B; Vandromme, A; Rodriguez-Faba, O; Marszalek, M

2013-06-01

About 70% of patients with renal cell carcinoma present with localized or locally advanced disease at primary diagnosis. Whereas these patients are potentially curable by surgical treatment alone, a further 20% to 30% of patients are diagnosed with primary metastatic disease. Although over the past years medical treatment for metastatic patients has nearly completely changed from immunotherapy to effective treatment with targeted agents, metastatic disease still represents a disease status which is not curable. Also in patients with metastatic disease, surgical treatment of the primary tumor plays an important role, since local tumor related complications can be avoided or minimized by surgery. Furthermore, also improvement of overall survival has been proven for surgery in metastatic patients when combined with cytokine treatment. Hence, surgical combined with systemic treatment as a multi-modal, adjuvant, and neo-adjuvant treatment is also required in patients with advanced or metastatic disease. A growing number of elderly and comorbid patients are currently diagnosed with small renal masses, which has led to increased attention paid to alternative ablative treatment modalities as well as active surveillance strategies, which are applied in order to avoid unnecessary overtreatment in these patients. Since surgical treatment also might enhance the risk of chronic kidney disease with consecutive cardiac disorders as well as reduced overall survival, ablative techniques and active surveillance are increasingly applied. In this review article we focus on current surgical and none-surgical treatment options for the management of patients with localized, locally advanced, and metastatic renal cell carcinoma.

Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research*

PubMed Central

Kuttykrishnan, Sooraj; Kalantar-Zadeh, Kamyar; Arah, Onyebuchi A.; Cheung, Alfred K.; Brunelli, Steve; Heagerty, Patrick J.; Katz, Ronit; Molnar, Miklos Z.; Nissenson, Allen; Ravel, Vanessa; Streja, Elani; Himmelfarb, Jonathan; Mehrotra, Rajnish

2015-01-01

Background The Institute of Medicine has identified the comparative effectiveness of renal replacement therapies as a kidney-related topic among the top 100 national priorities. Given the importance of ensuring internal and external validity, the goal of this study was to identify potential sources of bias in observational studies that compare outcomes with different dialysis modalities. Methods This observational cohort study used data from the electronic medical records of all patients that started maintenance dialysis in the calendar years 2007–2011 and underwent treatment for at least 60 days in any of the 2217 facilities operated by DaVita Inc. Each patient was assigned one of six dialysis modalities for each 91-day period from the date of first dialysis (thrice weekly in-center hemodialysis (HD), peritoneal dialysis (PD), less-frequent HD, home HD, frequent HD and nocturnal in-center HD). Results Of the 162 644 patients, 18% underwent treatment with a modality other than HD for at least one 91-day period. Except for PD, patients started treatment with alternative modalities after variable lengths of treatment with HD; the time until a change in modality was shortest for less-frequent HD (median time = 6 months) and longest for frequent HD (median time = 15 months). Between 30 and 78% of patients transferred to another dialysis facility prior to change in modality. Finally, there were significant differences in baseline and time-varying clinical characteristics associated with dialysis modality. Conclusions This analysis identified numerous potential sources of bias in studies of the comparative effectiveness of dialysis modalities. PMID:25883196

Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles

PubMed Central

Wen, Liewei; Yang, Sihua; Zhong, Junping; Zhou, Quan; Xing, Da

2017-01-01

Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy. PMID:28638483

Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles.

PubMed

Wen, Liewei; Yang, Sihua; Zhong, Junping; Zhou, Quan; Xing, Da

2017-01-01

Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy.

A geriatrician's guide to the use of the physical modalities in the treatment of pain and dysfunction.

PubMed

Perret, Danielle Marie; Rim, Josephine; Cristian, Adrian

2006-05-01

The use of the physical modalities in the treatment of musculoskeletal conditions has a long and rich history. This article explores the various physical modalities and their indications, precautions, and contraindications, especially in their applied use in pain management. It also highlights the role of the physical modalities as agents for the management of pain in the geriatric population.

The physiologic basis and clinical applications of cryotherapy and thermotherapy for the pain practitioner.

PubMed

Nadler, Scott F; Weingand, Kurt; Kruse, Roger J

2004-07-01

Cryotherapy and thermotherapy are useful adjuncts for the treatment of musculoskeletal injuries. Clinicians treating these conditions should be aware of current research findings regarding these modalities, because their choice of modality may affect the ultimate outcome of the patient being treated. Through a better understanding of these modalities, clinicians can optimize their present treatment strategies. Although cold and hot treatment modalities both decrease pain and muscle spasm, they have opposite effects on tissue metabolism, blood flow, inflammation, edema, and connective tissue extensibility. Cryotherapy decreases these effects while thermotherapy increases them. Continuous low-level cryotherapy and thermotherapy are newer concepts in therapeutic modalities. Both modalities provide significant pain relief with a low side-effect profile. Contrast therapy, which alternates between hot and cold treatment modalities, provides no additional therapeutic benefits compared with cryotherapy or thermotherapy alone. Complications of cryotherapy include nerve damage, frostbite, Raynaud's phenomenon, cold-induced urticaria, and slowed wound healing. With thermotherapy, skin burns may occur, especially in patients with diabetes mellitus, multiple sclerosis, poor circulation, and spinal cord injuries. In individuals with rheumatoid arthritis, deep-heating modalities should be used with caution because increased inflammation may occur. Whirlpool and other types of hydrotherapy have caused infections of the skin, urogenital, and pulmonary systems. Additionally, ultrasound should not be used in patients with joint prostheses.

Combined treatment modalities for age related macular degeneration.

PubMed

Das, R A; Romano, A; Chiosi, F; Menzione, M; Rinaldi, M

2011-02-01

Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.

Design of magnetic and fluorescent nanoparticles for in vivo MR and NIRF cancer imaging

NASA Astrophysics Data System (ADS)

Key, Jaehong

One big challenge for cancer treatment is that it has many errors in detection of cancers in the early stages before metastasis occurs. Using a current imaging modality, the detection of small tumors having potential metastasis is still very difficult. Thus, the development of multi-component nanoparticles (NPs) for dual modality cancer imaging is invaluable. The multi-component NPs can be an alternative to overcome the limitations from an imaging modality. For example, the multi-component NPs can visualize small tumors in both magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF) imaging, which can help find the location of the tumors deep inside the body using MRI and subsequently guide surgeons to delineate the margin of tumors using highly sensitive NIRF imaging during a surgical operation. In this dissertation, we demonstrated the potential of the MRI and NIRF dual-modality NPs for skin and bladder cancer imaging. The multi-component NPs consisted of glycol chitosan, superparamagnetic iron oxide, NIRF dye, and cancer targeting peptides. We characterized the NPs and evaluated them with tumor bearing mice as well as various cancer cells. The findings of this research will contribute to the development of cancer diagnostic imaging and it can also be extensively applied to drug delivery system and fluorescence-guided surgical removal of cancer.

Combined Auditory and Vibrotactile Feedback for Human-Machine-Interface Control.

PubMed

Thorp, Elias B; Larson, Eric; Stepp, Cara E

2014-01-01

The purpose of this study was to determine the effect of the addition of binary vibrotactile stimulation to continuous auditory feedback (vowel synthesis) for human-machine interface (HMI) control. Sixteen healthy participants controlled facial surface electromyography to achieve 2-D targets (vowels). Eight participants used only real-time auditory feedback to locate targets whereas the other eight participants were additionally alerted to having achieved targets with confirmatory vibrotactile stimulation at the index finger. All participants trained using their assigned feedback modality (auditory alone or combined auditory and vibrotactile) over three sessions on three days and completed a fourth session on the third day using novel targets to assess generalization. Analyses of variance performed on the 1) percentage of targets reached and 2) percentage of trial time at the target revealed a main effect for feedback modality: participants using combined auditory and vibrotactile feedback performed significantly better than those using auditory feedback alone. No effect was found for session or the interaction of feedback modality and session, indicating a successful generalization to novel targets but lack of improvement over training sessions. Future research is necessary to determine the cognitive cost associated with combined auditory and vibrotactile feedback during HMI control.

In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

PubMed Central

Zhang, Tao; Lan, Rongfeng; Chan, Chi-Fai; Law, Ga-Lai; Wong, Wai-Kwok; Wong, Ka-Leung

2014-01-01

In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy. PMID:25453097

Current and future medical treatments for patients with acromegaly.

PubMed

Maffezzoni, Filippo; Formenti, Anna Maria; Mazziotti, Gherardo; Frara, Stefano; Giustina, Andrea

2016-08-01

Acromegaly is a relatively rare condition of growth hormone (GH) excess associated with significant morbidity and, when left untreated, high mortality. Therapy for acromegaly is targeted at decreasing GH and insulin-like growth hormone 1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant) and radiotherapy. However, despite all these treatments option, approximately 50% of patients are not adequately controlled. In this paper, the authors discuss: 1) efficacy and safety of current medical therapy 2) the efficacy and safety of the new multireceptor-targeted somatostatin ligand pasireotide 3) medical treatments currently under clinical investigation (oral octreotide, ITF2984, ATL1103), and 4) preliminary data on the use of new injectable and transdermal/transmucosal formulations of octreotide. This expert opinion supports the need for new therapeutic agents and modalities for patients with acromegaly.

Modality comparison for small animal radiotherapy: A simulation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bazalova, Magdalena, E-mail: bazalova@stanford.edu; Nelson, Geoff; Noll, John M.

Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approaches—a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCTmore » scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. Conclusions: The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.« less

Axillary hyperhidrosis: A review of the extent of the problem and treatment modalities.

PubMed

Singh, Sanjay; Davis, Harriet; Wilson, Paul

2015-10-01

The purpose of this review is to summarize the extent of the problem of axillary hyperhidrosis and treatment modalities available. The benefits and disadvantages of various treatments are reflected on with the hope of providing a starting point to investigate new ways of treating hyperhidrosis. A literature search was conducted using various databases and search criteria. Current treatments include aluminium chloride antiperspirants, iontophoresis, botox injections and endoscopic thoracic sympathectomy. Botox therapy is usually the most effective treatment, without surgery or unpleasant side effects. However it has to be administered by a skilled clinician and involves around 20 injections to treat axillary hyperhidrosis. Other ways of giving Botox are being developed, the most promising one being the use of microneedles which are able to penetrate the skin and deliver drugs to the target area of the dermis without causing pain. In comparison to the temporary effects of microneedles, laser and microwave therapies are also assessed as they offer the hope of permanent relief from hyperhidrosis. There is a considerable dearth in the literature on the management of axillary hyperhidrosis. Further study in larger populations with longer follow up times is critical to access the long term effects of treatment. Microneedles could be the future treatment of choice with the potential to deliver drugs in a safe and pain free way. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Primary prevention of cannabis use: a systematic review of randomized controlled trials.

PubMed

Norberg, Melissa M; Kezelman, Sarah; Lim-Howe, Nicholas

2013-01-01

A systematic review of primary prevention was conducted for cannabis use outcomes in youth and young adults. The aim of the review was to develop a comprehensive understanding of prevention programming by assessing universal, targeted, uni-modal, and multi-modal approaches as well as individual program characteristics. Twenty-eight articles, representing 25 unique studies, identified from eight electronic databases (EMBASE, MEDLINE, CINAHL, ERIC, PsycINFO, DRUG, EBM Reviews, and Project CORK), were eligible for inclusion. Results indicated that primary prevention programs can be effective in reducing cannabis use in youth populations, with statistically significant effect sizes ranging from trivial (0.07) to extremely large (5.26), with the majority of significant effect sizes being trivial to small. Given that the preponderance of significant effect sizes were trivial to small and that percentages of statistically significant and non-statistically significant findings were often equivalent across program type and individual components, the effectiveness of primary prevention for cannabis use should be interpreted with caution. Universal multi-modal programs appeared to outperform other program types (i.e, universal uni-modal, targeted multi-modal, targeted unimodal). Specifically, universal multi-modal programs that targeted early adolescents (10-13 year olds), utilised non-teacher or multiple facilitators, were short in duration (10 sessions or less), and implemented boosters sessions were associated with large median effect sizes. While there were studies in these areas that contradicted these results, the results highlight the importance of assessing the interdependent relationship of program components and program types. Finally, results indicated that the overall quality of included studies was poor, with an average quality rating of 4.64 out of 9. Thus, further quality research and reporting and the development of new innovative programs are required.

Primary Prevention of Cannabis Use: A Systematic Review of Randomized Controlled Trials

PubMed Central

Norberg, Melissa M.; Kezelman, Sarah; Lim-Howe, Nicholas

2013-01-01

A systematic review of primary prevention was conducted for cannabis use outcomes in youth and young adults. The aim of the review was to develop a comprehensive understanding of prevention programming by assessing universal, targeted, uni-modal, and multi-modal approaches as well as individual program characteristics. Twenty-eight articles, representing 25 unique studies, identified from eight electronic databases (EMBASE, MEDLINE, CINAHL, ERIC, PsycINFO, DRUG, EBM Reviews, and Project CORK), were eligible for inclusion. Results indicated that primary prevention programs can be effective in reducing cannabis use in youth populations, with statistically significant effect sizes ranging from trivial (0.07) to extremely large (5.26), with the majority of significant effect sizes being trivial to small. Given that the preponderance of significant effect sizes were trivial to small and that percentages of statistically significant and non-statistically significant findings were often equivalent across program type and individual components, the effectiveness of primary prevention for cannabis use should be interpreted with caution. Universal multi-modal programs appeared to outperform other program types (i.e, universal uni-modal, targeted multi-modal, targeted unimodal). Specifically, universal multi-modal programs that targeted early adolescents (10–13 year olds), utilised non-teacher or multiple facilitators, were short in duration (10 sessions or less), and implemented boosters sessions were associated with large median effect sizes. While there were studies in these areas that contradicted these results, the results highlight the importance of assessing the interdependent relationship of program components and program types. Finally, results indicated that the overall quality of included studies was poor, with an average quality rating of 4.64 out of 9. Thus, further quality research and reporting and the development of new innovative programs are required. PMID:23326396

Effectiveness and Cost-effectiveness of Four Treatment Modalities for Substance Disorders: A Propensity Score Analysis

PubMed Central

Mojtabai, Ramin; Graff Zivin, Joshua

2003-01-01

Objective To assess the effectiveness and cost-effectiveness of four treatment modalities for substance abuse. Data Sources The study used data from the Services Research Outcomes Study (SROS), a survey of 3,047 clients in a random sample of 99 drug treatment facilities across the United States. Detailed sociodemographic, substance use, and clinical data were abstracted from treatment records. Substance abuse outcome and treatment history following discharge from index facilities were assessed using a comprehensive interview with 1,799 of these individuals five years after discharge. Treatment success was defined in two ways: as abstinence and as any reduction in substance use. Study Design Effectiveness and cost-effectiveness of four modalities were compared: inpatient, residential, outpatient detox/methadone, and outpatient drug-free. Clients were stratified based on propensity scores and analyses were conducted within these strata. Sensitivity analyses examined the impact of future substance abuse treatment on effectiveness and cost-effectiveness estimates. Principal Findings Treatment of substance disorders appears to be cost-effective compared to other health interventions. The cost per successfully treated abstinent case in the least costly modality, the outpatient drug-free programs, was $6,300 (95 percent confidence intervals: $5,200–$7,900) in 1990 dollars. There were only minor differences between various modalities of treatment with regard to effectiveness. However, modalities varied considerably with regard to cost-effectiveness. Outpatient drug-free programs were the most cost-effective. There was little evidence that relative effectiveness or cost-effectiveness of programs varied according to factors that were associated with selection into different programs. Conclusions Substance disorders can be treated most cost-effectively in outpatient drug-free settings. Savings from transitioning to the most cost-effective treatment modality may free resources that could be reinvested to improve access to substance abuse treatment for a larger number of individuals in need of such treatment. PMID:12650390

Managing Canine Aggression in the Home.

PubMed

Pike, Amy

2018-05-01

Canine aggression occurring in the home can be a dangerous diagnosis with costly consequences to all members of the household. Management is a key modality in the treatment of canine aggression in the home. A thorough history will detail each trigger, target, and context and allow for the veterinary team to put together a comprehensive management plan. Management allows for the avoidance of future aggressive episodes and minimizes the risks associated with living with a patient with these diagnoses. Although risk cannot be mitigated 100%, thorough management can create a safe environment for the implementation of the behavior treatment plan. Copyright © 2017 Elsevier Inc. All rights reserved.

The effectiveness of psychosocial modalities in the treatment of alcohol problems in adults: a review of the evidence.

PubMed

Martin, Garth W; Rehm, Jürgen

2012-06-01

Our objectives were to review the effectiveness of psychosocial modalities in the treatment of alcohol use disorders and problems, and to examine the impact of therapists on treatment outcome, the evidence on best practices for comorbid conditions, and the evidence on treatment matching. We based our review on published systematic reviews of this topic after 2000. There is strong evidence that some, but not all, psychosocial treatments are effective in treating alcohol problems. Those with the strongest empirical support are motivational enhancement therapy, various cognitive-behavioural interventions, and brief interventions. Meta-analyses for several of these modalities suggest typical effect sizes in the low-to-moderate range. When these modalities have been compared with one another in well-designed clinical trials, they have been shown to be of comparable effectiveness. There is little basis on which to recommend one of these modalities over another but good reason to select from among them.

SRT and SBRT: Current practices for QA dosimetry and 3D

NASA Astrophysics Data System (ADS)

Benedict, S. H.; Cai, J.; Libby, B.; Lovelock, M.; Schlesinger, D.; Sheng, K.; Yang, W.

2010-11-01

The major feature that separates stereotactic radiation therapy (cranial SRT) and stereotactic body radiation therapy (SBRT) from conventional radiation treatment is the delivery of large doses in a few fractions which results in a high biological effective dose (BED). In order to minimize the normal tissue toxicity, quality assurance of the conformation of high doses to the target and rapid fall off doses away from the target is critical. The practice of SRT and SBRT therefore requires a high-level of confidence in the accuracy of the entire treatment delivery process. In SRT and SBRT confidence in this accuracy is accomplished by the integration of modern imaging, simulation, treatment planning and delivery technologies into all phases of the treatment process; from treatment simulation and planning and continuing throughout beam delivery. In this report some of the findings of Task group 101 of the AAPM will be presented which outlines the best-practice guidelines for SBRT. The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information in this task group is provided for establishing an SBRT program, including protocols, equipment, resources, and QA procedures.

Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

PubMed

Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

2003-07-15

Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy?

PubMed

Kateb, Babak; Chiu, Katherine; Black, Keith L; Yamamoto, Vicky; Khalsa, Bhavraj; Ljubimova, Julia Y; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio; Modo, Mike; Moore, David F; Farahani, Keyvan; Okun, Michael S; Prakash, Neal; Neman, Josh; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D

2011-01-01

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines. Copyright © 2010 Elsevier Inc. All rights reserved.

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: What should be the policy?

PubMed Central

Kateb, Babak; Chiu, Katherine; Black, Keith L.; Yamamoto, Vicky; Khalsa, Bhavraj; Ljubimova, Julia Y.; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio; Modo, Mike; Moore, David F.; Farahani, Keyvan; Okun, Michael S.; Prakash, Neal; Neman, Josh; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D.

2012-01-01

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1–100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law–healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines. PMID:20149882

Mucosal melanoma of the head and neck: a systematic review of the literature.

PubMed

Lazarev, Stanislav; Gupta, Vishal; Hu, Kenneth; Harrison, Louis B; Bakst, Richard

2014-12-01

Primary mucosal melanoma of the head and neck (MMHN) comprises approximately 1% of all malignant melanomas. It presents more commonly in an elderly population and has no significant gender predominance. Given its rarity, most evidence of the causes, behavior, and treatment approaches for MMHN originates from isolated case reports and retrospective series. Between 1945 and 2011, at least 1951 cases of MMHN have been reported in the literature. Despite numerous technological developments in surgery and radiation therapy, as well as advances in systemic modalities, MMHN is an aggressive malignancy with a very poor prognosis. Complete surgical excision with clear margins remains the primary treatment modality. Adjuvant postoperative radiation therapy may improve locoregional control but does not appear to affect survival. Definitive particle radiation therapy promises to provide high rates of local control for nonoperable patients. Recent molecular evidence suggests that proto-oncogene KIT aberrations in a subset of mucosal melanomas may represent a potential diagnostic value and serve as a therapeutic target for tyrosine kinase inhibitors in an adjuvant setting for patients with advanced MMHN. Copyright © 2014 Elsevier Inc. All rights reserved.

Mucosal Melanoma of the Head and Neck: A Systematic Review of the Literature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lazarev, Stanislav; Gupta, Vishal; Hu, Kenneth

2014-12-01

Primary mucosal melanoma of the head and neck (MMHN) comprises approximately 1% of all malignant melanomas. It presents more commonly in an elderly population and has no significant gender predominance. Given its rarity, most evidence of the causes, behavior, and treatment approaches for MMHN originates from isolated case reports and retrospective series. Between 1945 and 2011, at least 1951 cases of MMHN have been reported in the literature. Despite numerous technological developments in surgery and radiation therapy, as well as advances in systemic modalities, MMHN is an aggressive malignancy with a very poor prognosis. Complete surgical excision with clear marginsmore » remains the primary treatment modality. Adjuvant postoperative radiation therapy may improve locoregional control but does not appear to affect survival. Definitive particle radiation therapy promises to provide high rates of local control for nonoperable patients. Recent molecular evidence suggests that proto-oncogene KIT aberrations in a subset of mucosal melanomas may represent a potential diagnostic value and serve as a therapeutic target for tyrosine kinase inhibitors in an adjuvant setting for patients with advanced MMHN.« less

Occipital Neuralgia Diagnosis and Treatment: The Role of Ultrasound.

PubMed

Narouze, Samer

2016-04-01

Occipital neuralgia is a form of neuropathic type of pain in the distribution of the greater, lesser, or third occipital nerves. Patients with intractable occipital neuralgia do not respond well to conservative treatment modalities. This group of patients represents a significant therapeutic challenge and may require interventional or invasive therapeutic approaches. Occipital neuralgia frequently occurs as a result of nerve entrapment or irritation by a tight muscle or vascular structure, or nerve trauma during whiplash injury. Although the entrapment theory is most commonly accepted, it lacks strong clinical evidence to support it. Accordingly, the available interventional approaches have been targeting the accessible part of the occipital nerve rather than the entrapped part. Bedside sonography is an excellent imaging modality for soft tissue structures. Ultrasound not only allows distinguishing normal from abnormal entrapped occipital nerves, it can identify the level and the cause of entrapment as well. Ultrasound guidance allows precise occipital nerve blocks and interventions at the level of the "specific" entrapment location rather than into the site of "presumed" entrapment. © 2016 American Headache Society.

Olminska and colleagues' study, "Conversion of the helical tomotherapy plans to the step-and-shoot IMRT plans for patients with hip prosthesis during radiotherapy for prostate cancer" was interesting to read.

PubMed

Cihan, Yasemin Benderli

2016-11-01

Olmińska and colleagues' study, Olmińska et al. (2016) was interesting to read [1]. While prasining the authors for their great work, I want to emphasize e few points. In the recent years, with the development of new device technology, Intensity Modulated Radiotherapy (IMRT) and complex treatment modalities such as stereotactic radiosurgery and helical tomotherapy were started to be implemented. Thus, due to increased local control of tumor growth and reduction of dose received by surrounding critical organs, serious complications were avoided. In this new treatment modality, while calculating appropriate dose, all the parameters such as patient anatomy and characteristics of radiation should be taken into account. Besides, during conformal radiotherapy, if hip prosthesis is located around or in the clinical target volume (CTV), type, thickness and density of biomaterial should be considered to avoid dose differences. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Psychological trauma symptoms and Type 2 diabetes prevalence, glucose control, and treatment modality among American Indians in the Strong Heart Family Study

PubMed Central

Jacob, Michelle M.; Gonzales, Kelly L.; Calhoun, Darren; Beals, Janette; Muller, Clemma Jacobsen; Goldberg, Jack; Nelson, Lonnie; Welty, Thomas K.; Howard, Barbara V.

2013-01-01

Aims The aims of this paper are to examine the relationship between psychological trauma symptoms and Type 2 diabetes prevalence, glucose control, and treatment modality among 3,776 American Indians in Phase V of the Strong Heart Family Study. Methods This cross-sectional analysis measured psychological trauma symptoms using the National Anxiety Disorder Screening Day instrument, diabetes by American Diabetes Association criteria, and treatment modality by four categories: no medication, oral medication only, insulin only, or both oral medication and insulin. We used binary logistic regression to evaluate the association between psychological trauma symptoms and diabetes prevalence. We used ordinary least squares regression to evaluate the association between psychological trauma symptoms and glucose control. We used binary logistic regression to model the association of psychological trauma symptoms with treatment modality. Results Neither diabetes prevalence (22-31%; p = 0.19) nor control (8.0-8.6; p = 0.25) varied significantly by psychological trauma symptoms categories. However, diabetes treatment modality was associated with psychological trauma symptoms categories, as people with greater burden used either no medication, or both oral and insulin medications (odds ratio = 3.1, p < 0.001). Conclusions The positive relationship between treatment modality and psychological trauma symptoms suggests future research investigate patient and provider treatment decision making. PMID:24051029

SU-E-J-33: Comparison Between Soft Tissue Alignment and Bony Alignment for Pancreatic Cancer Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suh, Y; Crane, C; Krishnan, S

Purpose An IGRT modality for pancreatic cancer treatment with dose escalation at our institution is in-room daily CT imaging. The purpose of this study is to assess the difference between soft tissue alignment and bony alignment for pancreatic tumor localization. Methods Eighteen patients with pancreatic tumors who underwent IMRT treatment with an inspiration breath-hold technique between July 2012 and February 2015 are included in this study. Prior to each treatment, a CT scan was acquired. The CT image guidance started with auto-alignment to either the bony anatomy (vertebral bodies) or fiducials (for the six patients with the stent in/near themore » tumor) and then, when necessary, manual adjustments were made based on soft tissue alignment using clinical software (CT-Assisted Targeting system). The difference between soft tissue alignment and bony/fiducial alignment was evaluated. Results Of all 380 treatments, manual adjustment was made in 225 treatments, ranging from 11% (3 treatments out of 28) to 96% (27 treatments out of 28) per patient. The mean of the difference between soft tissue alignment and bony/fiducial alignment per patient ranged from −3.6 to 0.3 mm, −1.5 to 2.8 mm, and −3.3 to 3.4 mm in the AP, SI, and RL directions, respectively. The maximum difference over all treatments was −9.5, −14.6, and −14.6 mm in the AP, SI, and RL directions, respectively. Conclusion About 60% of the time, manual adjustment based on soft tissue alignment was required. The extent of manual adjustment was usually small but varied significantly from patient to patient. The ultimate goal of the IGRT modality using daily CT imaging is not to fully cover the target but to spare organs-at-risk as much as possible to avoid them moving into higher dose gradients than accepted in the treatment plan. To this end, manual adjustment based on soft tissue alignment is critically important.« less

Transcutaneous laser treatment of leg veins.

PubMed

Meesters, Arne A; Pitassi, Luiza H U; Campos, Valeria; Wolkerstorfer, Albert; Dierickx, Christine C

2014-03-01

Leg telangiectasias and reticular veins are a common complaint affecting more than 80% of the population to some extent. To date, the gold standard remains sclerotherapy for most patients. However, there may be some specific situations, where sclerotherapy is contraindicated such as needle phobia, allergy to certain sclerosing agents, and the presence of vessels smaller than the diameter of a 30-gauge needle (including telangiectatic matting). In these cases, transcutaneous laser therapy is a valuable alternative. Currently, different laser modalities have been proposed for the management of leg veins. The aim of this article is to present an overview of the basic principles of transcutaneous laser therapy of leg veins and to review the existing literature on this subject, including the most recent developments. The 532-nm potassium titanyl phosphate (KTP) laser, the 585-600-nm pulsed dye laser, the 755-nm alexandrite laser, various 800-983-nm diode lasers, and the 1,064-nm neodymium yttrium-aluminum-garnet (Nd:YAG) laser and various intense pulsed light sources have been investigated for this indication. The KTP and pulsed dye laser are an effective treatment option for small vessels (<1 mm). The side effect profile is usually favorable to that of longer wavelength modalities. For larger veins, the use of a longer wavelength is required. According to the scarce evidence available, the Nd:YAG laser produces better clinical results than the alexandrite and diode laser. Penetration depth is high, whereas absorption by melanin is low, making the Nd:YAG laser suitable for the treatment of larger and deeply located veins and for the treatment of patients with dark skin types. Clinical outcome of Nd:YAG laser therapy approximates that of sclerotherapy, although the latter is associated with less pain. New developments include (1) the use of a nonuniform pulse sequence or a dual-wavelength modality, inducing methemoglobin formation and enhancing the optical absorption properties of the target structure, (2) pulse stacking and multiple pass laser treatment, (3) combination of laser therapy with sclerotherapy or radiofrequency, and (4) indocyanin green enhanced laser therapy. Future studies will have to confirm the role of these developments in the treatment of leg veins. The literature still lacks double-blind controlled clinical trials comparing the different laser modalities with each other and with sclerotherapy. Such trials should be the focus of future research.

Comparison of Transcutaneous Electrical Nerve Stimulation and Cryotherapy for Increasing Quadriceps Activation in Patients With Knee Pathologies.

PubMed

Gabler, Conrad M; Lepley, Adam S; Uhl, Tim L; Mattacola, Carl G

2016-08-01

Proper neuromuscular activation of the quadriceps muscle is essential for maintaining quadriceps (quad) strength and lower-extremity function. Quad activation (QA) failure is a common characteristic observed in patients with knee pathologies, defined as an inability to voluntarily activate the entire alpha-motor-neuron pool innervating the quad. One of the more popular techniques used to assess QA is the superimposed burst (SIB) technique, a force-based technique that uses a supramaximal, percutaneous electrical stimulation to activate all of the motor units in the quad during a maximal, voluntary isometric contraction. Central activation ratio (CAR) is the formula used to calculate QA level (CAR = voluntary force/SIB force) with the SIB technique. People who can voluntarily activate 95% or more (CAR = 0.95-1.0) of their motor units are defined as being fully activated. Therapeutic exercises aimed at improving quad strength in patients with knee pathologies are limited in their effectiveness due to a failure to fully activate the muscle. Within the past decade, several disinhibitory interventions have been introduced to treat QA failure in patients with knee pathologies. Transcutaneous electrical nerve stimulation (TENS) and cryotherapy are sensory-targeted modalities traditionally used to treat pain, but they have been shown to be 2 of the most successful treatments for increasing QA levels in patients with QA failure. Both modalities are hypothesized to positively affect voluntary QA by disinhibiting the motor-neuron pool of the quad. In essence, these modalities provide excitatory afferent stimuli to the spinal cord, which thereby overrides the inhibitory afferent signaling that arises from the involved joint. However, it remains unknown whether 1 is more effective than the other for restoring QA levels in patients with knee pathologies. By knowing the capabilities of each disinhibitory modality, clinicians can tailor treatments based on the rehabilitation goals of their patients. Focused Clinical Question: Is TENS or cryotherapy the more effective disinhibitory modality for treating QA failure (quantified via CAR) in patients with knee pathologies?

SU-F-J-160: Clinical Evaluation of Targeting Accuracy in Radiosurgery Using Tractography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juh, R; Han, J; Kim, C

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 males, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve. Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement. Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.« less

SU-E-J-34: Clinical Evaluation of Targeting Accuracy and Tractogrphy Delineation of Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juh, R; Suh, T; Kim, Y

2014-06-01

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 male, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve . Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.« less

Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research.

PubMed

Kuttykrishnan, Sooraj; Kalantar-Zadeh, Kamyar; Arah, Onyebuchi A; Cheung, Alfred K; Brunelli, Steve; Heagerty, Patrick J; Katz, Ronit; Molnar, Miklos Z; Nissenson, Allen; Ravel, Vanessa; Streja, Elani; Himmelfarb, Jonathan; Mehrotra, Rajnish

2015-07-01

The Institute of Medicine has identified the comparative effectiveness of renal replacement therapies as a kidney-related topic among the top 100 national priorities. Given the importance of ensuring internal and external validity, the goal of this study was to identify potential sources of bias in observational studies that compare outcomes with different dialysis modalities. This observational cohort study used data from the electronic medical records of all patients that started maintenance dialysis in the calendar years 2007-2011 and underwent treatment for at least 60 days in any of the 2217 facilities operated by DaVita Inc. Each patient was assigned one of six dialysis modalities for each 91-day period from the date of first dialysis (thrice weekly in-center hemodialysis (HD), peritoneal dialysis (PD), less-frequent HD, home HD, frequent HD and nocturnal in-center HD). Of the 162 644 patients, 18% underwent treatment with a modality other than HD for at least one 91-day period. Except for PD, patients started treatment with alternative modalities after variable lengths of treatment with HD; the time until a change in modality was shortest for less-frequent HD (median time = 6 months) and longest for frequent HD (median time = 15 months). Between 30 and 78% of patients transferred to another dialysis facility prior to change in modality. Finally, there were significant differences in baseline and time-varying clinical characteristics associated with dialysis modality. This analysis identified numerous potential sources of bias in studies of the comparative effectiveness of dialysis modalities. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Temperature distribution in target tumor tissue and photothermal tissue destruction during laser immunotherapy

NASA Astrophysics Data System (ADS)

Doughty, Austin; Hasanjee, Aamr; Pettitt, Alex; Silk, Kegan; Liu, Hong; Chen, Wei R.; Zhou, Feifan

2016-03-01

Laser Immunotherapy is a novel cancer treatment modality that has seen much success in treating many different types of cancer, both in animal studies and in clinical trials. The treatment consists of the synergistic interaction between photothermal laser irradiation and the local injection of an immunoadjuvant. As a result of the therapy, the host immune system launches a systemic antitumor response. The photothermal effect induced by the laser irradiation has multiple effects at different temperature elevations which are all required for optimal response. Therefore, determining the temperature distribution in the target tumor during the laser irradiation in laser immunotherapy is crucial to facilitate the treatment of cancers. To investigate the temperature distribution in the target tumor, female Wistar Furth rats were injected with metastatic mammary tumor cells and, upon sufficient tumor growth, underwent laser irradiation and were monitored using thermocouples connected to locally-inserted needle probes and infrared thermography. From the study, we determined that the maximum central tumor temperature was higher for tumors of less volume. Additionally, we determined that the temperature near the edge of the tumor as measured with a thermocouple had a strong correlation with the maximum temperature value in the infrared camera measurement.

Molecular Biology of Lung Cancer

PubMed Central

Nana-Sinkam, Serge Patrick

2013-01-01

Based on recent bench and clinical research, the treatment of lung cancer has been refined, with treatments allocated according to histology and specific molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors has been particularly successful as a treatment modality, demonstrating response rates in selected patients with adenocarcinoma tumors harboring EGFR mutations that are significantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, and the development of highly reproducible platforms for high-throughput biomarker discovery and testing. In this article, we review clinically relevant research directed toward understanding the biology of lung cancer. The clinical purposes of this research are (1) to identify susceptibility variants and field molecular alterations that will promote the early detection of tumors and (2) to identify tumor molecular alterations that serve as therapeutic targets, prognostic biomarkers, or predictors of tumor response. We focus on research developments in the understanding of lung cancer somatic DNA mutations, chromosomal aberrations, epigenetics, and the tumor microenvironment, and how they can advance diagnostics and therapeutics. PMID:23649444

The Role of Interventional Oncology in the Management of Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duka, Ejona, E-mail: ejonaduka@hotmail.com; Ierardi, Anna Maria, E-mail: amierardi@yahoo.it; Floridi, Chiara, E-mail: chiara.floridi@gmail.com

Interventional radiological procedures for diagnosis and treatment of lung cancer have become increasingly important. Imaging-guided percutaneous biopsy has become the modality of choice for diagnosing lung cancer, and in the era of target therapies, it is an useful tool to define earlier patient-specific tumor phenotypes. In functionally inoperable patients, especially the ablative procedures are potentially curative alternatives to surgery. In addition to thermally ablative treatment, selective chemoembolization by a vascular access allows localized therapy. These treatments are considered for patients in a reduced general condition which does not allow systemic chemotherapy. The present article reviews the role of interventional oncologymore » in the management of primary lung cancer, focusing on the state of the art for each procedure.« less

Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.

PubMed

Ouzzane, Adil; Betrouni, Nacim; Valerio, Massimo; Rastinehad, Ardeshir; Colin, Pierre; Ploussard, Guillaume

2017-04-01

Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.

Improving Atrial Fibrillation Therapy: Is There a Gene for That?

PubMed

Hucker, William J; Hanley, Alan; Ellinor, Patrick T

2017-04-25

Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment. In this review, we summarize the available published data on gene therapy and discuss the challenges, opportunities, and limitations of this approach. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Melasma update

PubMed Central

Sarkar, Rashmi; Arora, Pooja; Garg, Vijay Kumar; Sonthalia, Sidharth; Gokhale, Narendra

2014-01-01

Melasma is an acquired pigmentary disorder characterized by symmetrical hyperpigmented macules on the face. Its pathogenesis is complex and involves the interplay of various factors such as genetic predisposition, ultraviolet radiation, hormonal factors, and drugs. An insight into the pathogenesis is important to devise treatment modalities that accurately target the disease process and prevent relapses. Hydroquinone remains the gold standard of treatment though many newer drugs, especially plant extracts, have been developed in the last few years. In this article, we review the pathogenetic factors involved in melasma. We also describe the newer treatment options available and their efficacy. We carried out a PubMed search using the following terms “melasma, pathogenesis, etiology, diagnosis, treatment” and have included data of the last few years. PMID:25396123

Children's On-Line Processing of Epistemic Modals

ERIC Educational Resources Information Center

Moscati, Vincenzo; Zhan, Likan; Zhou, Peng

2017-01-01

In this paper we investigated the real-time processing of epistemic modals in five-year-olds. In a simple reasoning scenario, we monitored children's eye-movements while processing a sentence with modal expressions of different force ("might/must"). Children were also asked to judge the truth-value of the target sentences at the end of…

A Comparison of Therapeutic Factors in Two Group Treatment Modalities: Verbal and Art Therapy.

ERIC Educational Resources Information Center

Shechtman, Zipora; Perl-Dekel, Ofra

2000-01-01

Compares therapeutic factors in verbal and art group psychotherapy in a psychiatric day-treatment clinic in Israel. Results only partly support the differences between modalities, but do reveal significant differences between participants with only a few interactions between participants and modalities. All therapeutic factors appear in both…

Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals

PubMed Central

Longmire, Michelle R.; Ogawa, Mikako; Choyke, Peter L.

2012-01-01

In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references). PMID:21607237

In vivo tumor-targeted dual-modal fluorescence/CT imaging using a nanoprobe co-loaded with an aggregation-induced emission dye and gold nanoparticles.

PubMed

Zhang, Jimei; Li, Chan; Zhang, Xu; Huo, Shuaidong; Jin, Shubin; An, Fei-Fei; Wang, Xiaodan; Xue, Xiangdong; Okeke, C I; Duan, Guiyun; Guo, Fengguang; Zhang, Xiaohong; Hao, Jifu; Wang, Paul C; Zhang, Jinchao; Liang, Xing-Jie

2015-02-01

As an intensely studied computed tomography (CT) contrast agent, gold nanoparticle has been suggested to be combined with fluorescence imaging modality to offset the low sensitivity of CT. However, the strong quenching of gold nanoparticle on fluorescent dyes requires complicated design and shielding to overcome. Herein, we report a unique nanoprobe (M-NPAPF-Au) co-loading an aggregation-induced emission (AIE) red dye and gold nanoparticles into DSPE-PEG(2000) micelles for dual-modal fluorescence/CT imaging. The nanoprobe was prepared based on a facile method of "one-pot ultrasonic emulsification". Surprisingly, in the micelles system, fluorescence dye (NPAPF) efficiently overcame the strong fluorescence quenching of shielding-free gold nanoparticles and retained the crucial AIE feature. In vivo studies demonstrated the nanoprobe had superior tumor-targeting ability, excellent fluorescence and CT imaging effects. The totality of present studies clearly indicates the significant potential application of M-NPAPF-Au as a dual-modal non-invasive fluorescence/X-ray CT nanoprobe for in vivo tumor-targeted imaging and diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Physician perceptions of the value of physical modalities in the treatment of musculoskeletal disease.

PubMed

Rush, P J; Shore, A

1994-06-01

We randomly surveyed 100 specialists in rehabilitation medicine and 100 rheumatologists concerning their perceptions of the value of 11 different physical modalities--cold, active and passive exercise, interferential current, laser, magnetotherapy, microwave, shortwave diathermy, traction, ultrasound and transcutaneous nerve stimulation in the treatment of seven different musculoskeletal conditions--acute arthritis, joint contracture, neck pain, back pain, tendinitis, reflex sympathetic dystrophy and frozen shoulder. There were significant differences in the perceived benefits of modalities which varied by modality and condition. Overall, rehabilitation medicine specialists regarded modalities to be helpful more often than rheumatologists (P < 0.001).

Monte Carlo treatment planning with modulated electron radiotherapy: framework development and application

NASA Astrophysics Data System (ADS)

Alexander, Andrew William

Within the field of medical physics, Monte Carlo radiation transport simulations are considered to be the most accurate method for the determination of dose distributions in patients. The McGill Monte Carlo treatment planning system (MMCTP), provides a flexible software environment to integrate Monte Carlo simulations with current and new treatment modalities. A developing treatment modality called energy and intensity modulated electron radiotherapy (MERT) is a promising modality, which has the fundamental capabilities to enhance the dosimetry of superficial targets. An objective of this work is to advance the research and development of MERT with the end goal of clinical use. To this end, we present the MMCTP system with an integrated toolkit for MERT planning and delivery of MERT fields. Delivery is achieved using an automated "few leaf electron collimator" (FLEC) and a controller. Aside from the MERT planning toolkit, the MMCTP system required numerous add-ons to perform the complex task of large-scale autonomous Monte Carlo simulations. The first was a DICOM import filter, followed by the implementation of DOSXYZnrc as a dose calculation engine and by logic methods for submitting and updating the status of Monte Carlo simulations. Within this work we validated the MMCTP system with a head and neck Monte Carlo recalculation study performed by a medical dosimetrist. The impact of MMCTP lies in the fact that it allows for systematic and platform independent large-scale Monte Carlo dose calculations for different treatment sites and treatment modalities. In addition to the MERT planning tools, various optimization algorithms were created external to MMCTP. The algorithms produced MERT treatment plans based on dose volume constraints that employ Monte Carlo pre-generated patient-specific kernels. The Monte Carlo kernels are generated from patient-specific Monte Carlo dose distributions within MMCTP. The structure of the MERT planning toolkit software and optimization algorithms are demonstrated. We investigated the clinical significance of MERT on spinal irradiation, breast boost irradiation, and a head and neck sarcoma cancer site using several parameters to analyze the treatment plans. Finally, we investigated the idea of mixed beam photon and electron treatment planning. Photon optimization treatment planning tools were included within the MERT planning toolkit for the purpose of mixed beam optimization. In conclusion, this thesis work has resulted in the development of an advanced framework for photon and electron Monte Carlo treatment planning studies and the development of an inverse planning system for photon, electron or mixed beam radiotherapy (MBRT). The justification and validation of this work is found within the results of the planning studies, which have demonstrated dosimetric advantages to using MERT or MBRT in comparison to clinical treatment alternatives.

Parallel perceptual enhancement and hierarchic relevance evaluation in an audio-visual conjunction task.

PubMed

Potts, Geoffrey F; Wood, Susan M; Kothmann, Delia; Martin, Laura E

2008-10-21

Attention directs limited-capacity information processing resources to a subset of available perceptual representations. The mechanisms by which attention selects task-relevant representations for preferential processing are not fully known. Triesman and Gelade's [Triesman, A., Gelade, G., 1980. A feature integration theory of attention. Cognit. Psychol. 12, 97-136.] influential attention model posits that simple features are processed preattentively, in parallel, but that attention is required to serially conjoin multiple features into an object representation. Event-related potentials have provided evidence for this model showing parallel processing of perceptual features in the posterior Selection Negativity (SN) and serial, hierarchic processing of feature conjunctions in the Frontal Selection Positivity (FSP). Most prior studies have been done on conjunctions within one sensory modality while many real-world objects have multimodal features. It is not known if the same neural systems of posterior parallel processing of simple features and frontal serial processing of feature conjunctions seen within a sensory modality also operate on conjunctions between modalities. The current study used ERPs and simultaneously presented auditory and visual stimuli in three task conditions: Attend Auditory (auditory feature determines the target, visual features are irrelevant), Attend Visual (visual features relevant, auditory irrelevant), and Attend Conjunction (target defined by the co-occurrence of an auditory and a visual feature). In the Attend Conjunction condition when the auditory but not the visual feature was a target there was an SN over auditory cortex, when the visual but not auditory stimulus was a target there was an SN over visual cortex, and when both auditory and visual stimuli were targets (i.e. conjunction target) there were SNs over both auditory and visual cortex, indicating parallel processing of the simple features within each modality. In contrast, an FSP was present when either the visual only or both auditory and visual features were targets, but not when only the auditory stimulus was a target, indicating that the conjunction target determination was evaluated serially and hierarchically with visual information taking precedence. This indicates that the detection of a target defined by audio-visual conjunction is achieved via the same mechanism as within a single perceptual modality, through separate, parallel processing of the auditory and visual features and serial processing of the feature conjunction elements, rather than by evaluation of a fused multimodal percept.

Comparative analysis of success of psoriasis treatment with standard therapeutic modalities and balneotherapy.

PubMed

Baros, Duka Ninković; Gajanin, Vesna S; Gajanin, Radoslav B; Zrnić, Bogdan

2014-01-01

Psoriasis is a chronic, inflammatory, immune-mediated skin disease. In addition to standard therapeutic modalities (antibiotics, cytostatics, phototherapy, photochemotherapy and retinoids), nonstandard methods can be used in the treatment of psoriasis. This includes balneotherapy which is most commonly used in combination with therapeutic resources. The aim of this research was to determine the length of remission of psoriasis in patients treated with standard therapeutic modalities, balneotherapy, and combined treatment (standard therapeutic modalities and balneotherapy). The study analyzed 60 adult patients, of both sexes, with different clinical forms of psoriasis, who were divided into three groups according to the applied therapeutic modalities: the first group (treated with standard therapeutic modalities), the second group (treated with balneotherapy) and the third group (treated with combined therapy-standard methods therapy and balneotherapy). The Psoriasis Area and Severity Index was determined in first, third and sixth week of treatment for all patients. The following laboratory analysis were performed and monitored: C reactive protein, iron with total iron binding capacity, unsaturated iron binding capacity and ferritin, uric acid, rheumatoid factors and antibodies to streptolysin O in the first and sixth week of treatment. The average length of remission in patients treated with standard therapeutic modalities and in those treated with balneotherapy was 1.77 +/- 0.951 months and 1.79 +/- 0.918 months, respectively. There was a statistically significant difference in the duration of remission between the patients treated with combination therapy and patients treated with standard therapeutic modalities (p = 0.019) and balneotherapy (p = 0.032). The best results have been achieved when the combination therapy was administered.

Spatial Analysis of Case-Mix and Dialysis Modality Associations.

PubMed

Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

2016-01-01

♦ Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be evaluated in terms of patients' quality of life, satisfaction, survival, and global efficiency. Copyright © 2016 International Society for Peritoneal Dialysis.

Spatial Analysis of Case-Mix and Dialysis Modality Associations

PubMed Central

Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

2016-01-01

♦ Background: Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ Methods: The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ Result: The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ Conclusions: The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be evaluated in terms of patients' quality of life, satisfaction, survival, and global efficiency. PMID:26475843

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

PubMed Central

Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

2013-01-01

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT. PMID:26229621

Dynamic Facial Expressions Prime the Processing of Emotional Prosody.

PubMed

Garrido-Vásquez, Patricia; Pell, Marc D; Paulmann, Silke; Kotz, Sonja A

2018-01-01

Evidence suggests that emotion is represented supramodally in the human brain. Emotional facial expressions, which often precede vocally expressed emotion in real life, can modulate event-related potentials (N100 and P200) during emotional prosody processing. To investigate these cross-modal emotional interactions, two lines of research have been put forward: cross-modal integration and cross-modal priming. In cross-modal integration studies, visual and auditory channels are temporally aligned, while in priming studies they are presented consecutively. Here we used cross-modal emotional priming to study the interaction of dynamic visual and auditory emotional information. Specifically, we presented dynamic facial expressions (angry, happy, neutral) as primes and emotionally-intoned pseudo-speech sentences (angry, happy) as targets. We were interested in how prime-target congruency would affect early auditory event-related potentials, i.e., N100 and P200, in order to shed more light on how dynamic facial information is used in cross-modal emotional prediction. Results showed enhanced N100 amplitudes for incongruently primed compared to congruently and neutrally primed emotional prosody, while the latter two conditions did not significantly differ. However, N100 peak latency was significantly delayed in the neutral condition compared to the other two conditions. Source reconstruction revealed that the right parahippocampal gyrus was activated in incongruent compared to congruent trials in the N100 time window. No significant ERP effects were observed in the P200 range. Our results indicate that dynamic facial expressions influence vocal emotion processing at an early point in time, and that an emotional mismatch between a facial expression and its ensuing vocal emotional signal induces additional processing costs in the brain, potentially because the cross-modal emotional prediction mechanism is violated in case of emotional prime-target incongruency.

Strategic management of keloid disease in ethnic skin: a structured approach supported by the emerging literature.

PubMed

Ud-Din, S; Bayat, A

2013-10-01

Keloid disease (KD) is a common, benign, dermal fibroproliferative growth of unknown aetiology. Lesions tend to grow over time; they often recur following therapy and do not regress spontaneously. KD causes considerable discomfort due to pain, pruritus and inflammation, and a significant psychosocial impact with reduced quality of life. It is unique to humans and occurrence is higher in individuals with dark, pigmented, ethnic skin. There is a strong familial heritability, with a high ethnic predisposition in individuals of African, Asian and Hispanic descent. High recurrence rates and unknown resolution rates present a major problem for both the patient and clinician. Many treatment modalities exist; however, there is no single advocated therapy. Therefore, the aim of this review was to explore the most current literature regarding the range of treatment options for KD and to offer a structured approach in the management of KD, based on evidence and experience, to aid clinicians in their current practice. A focused history involving careful evaluation of the patient's symptoms, signs, quality of life and psychosocial well-being should direct targeted therapy, complemented with regular follow-up and re-evaluation. Many treatment modalities, such as intralesional steroid injection, silicone gel application, cryotherapy, lasers, 5-fluorouracil and, relatively recently, photodynamic therapy, are currently being used in clinical practice for the management of KD. Combination therapies have also been shown to be beneficial. However, there is a lack of robust, randomized, level-one, evidence-controlled trials evaluating these treatment options. Management of KD in ethnic pigmented skin remains a clinical challenge. Thus, a strategic approach with structured assessment, targeted therapy and focus on prevention of recurrence is highly recommended. Quality evidence is essential in order to tailor treatment effectively for the ethnic patient presenting with KD. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan comparison between VHEE, VMAT, and PPBS.

PubMed

Schüler, Emil; Eriksson, Kjell; Hynning, Elin; Hancock, Steven L; Hiniker, Susan M; Bazalova-Carter, Magdalena; Wong, Tony; Le, Quynh-Thu; Loo, Billy W; Maxim, Peter G

2017-06-01

The aim of this study was to evaluate the performance of very high-energy electron beams (VHEE) in comparison to clinically derived treatment plans generated with volumetric modulated arc therapy (VMAT) and proton pencil beam scanning (PPBS) technology. We developed a custom optimization script that could be applied automatically across modalities to eliminate operator bias during IMRT optimization. Four clinical cases were selected (prostate cancer, lung cancer, pediatric brain tumor, and head and neck cancer (HNC)). The VHEE beams were calculated in the EGSnrc/DOSXYZnrc Monte Carlo code for 100 and 200 MeV beams. Treatment plans with VHEE, VMAT, and PPBS were optimized in a research version of RayStation using an in-house developed script to minimize operator bias between the different techniques. The in-house developed script generated similar or superior plans to the clinically used plans. In the comparisons between the modalities, the integral dose was lowest for the PPBS-generated plans in all cases. For the prostate case, the 200 MeV VHEE plan showed reduced integral dose and reduced organ at risk (OAR) dose compared to the VMAT plan. For all other cases, both the 100 and the 200 MeV VHEE plans were superior to the VMAT plans, and the VHEE plans showed better conformity and lower spinal cord dose in the pediatric brain case and lower brain stem dose in the HNC case when compared to the PPBS plan. The automated optimization developed in this study generated similar or superior plans as compared to the clinically used plan and represents an unbiased approach to compare treatment plans generated for different modalities. In the present study, we also show that VHEE plans are similar or superior to VMAT plans with reduced mean OAR dose and increased target conformity for a variety of clinical cases, and VHEE plans can even achieve reductions in OAR doses compared to PPBS plans for shallow targets. With increased VHEE energy, better conformity and even higher reductions in mean OAR doses are achieved. On the whole, VHEE was intermediate between photon VMAT and PPBS for OAR sparing. © 2017 American Association of Physicists in Medicine.

Different treatment modalities of fusiform basilar trunk aneurysm: study on computational hemodynamics.

PubMed

Wu, Chen; Xu, Bai-Nan; Sun, Zheng-Hui; Wang, Fu-Yu; Liu, Lei; Zhang, Xiao-Jun; Zhou, Ding-Biao

2012-01-01

Unclippable fusiform basilar trunk aneurysm is a formidable condition for surgical treatment. The aim of this study was to establish a computational model and to investigate the hemodynamic characteristics in a fusiform basilar trunk aneurysm. The three-dimensional digital model of a fusiform basilar trunk aneurysm was constructed using MIMICS, ANSYS and CFX software. Different hemodynamic modalities and border conditions were assigned to the model. Thirty points were selected randomly on the wall and within the aneurysm. Wall total pressure (WTP), wall shear stress (WSS), and blood flow velocity of each point were calculated and hemodynamic status was compared between different modalities. The quantitative average values of the 30 points on the wall and within the aneurysm were obtained by computational calculation point by point. The velocity and WSS in modalities A and B were different from those of the remaining 5 modalities; and the WTP in modalities A, E and F were higher than those of the remaining 4 modalities. The digital model of a fusiform basilar artery aneurysm is feasible and reliable. This model could provide some important information to clinical treatment options.

Monitoring femtosecond laser microscopic photothermolysis with multimodal microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Huang, Yimei; Lui, Harvey; Zhao, Jianhua; McLean, David I.; Zeng, Haishan

2016-02-01

Photothermolysis induced by femtosecond (fs) lasers may be a promising modality in dermatology because of its advantages of high precision due to multiphoton absorption and deeper penetration due to the use of near infrared wavelengths. Although multiphoton absorption nonlinear effects are capable of precision targeting, the femtosecond laser photothermolysis could still have effects beyond the targeted area if a sufficiently high dose of laser light is used. Such unintended effects could be minimized by real time monitoring photothermolysis during the treatment. Targeted photothermolytic treatment of ex vivo mouse skin dermis was performed with tightly focused fs laser beams. Images of reflectance confocal microscopy (RCM), second harmonic generation (SHG), and two-photon fluorescence (TPF) of the mouse skins were obtained with integrated multimodal microscopy before, during, and after the laser treatment. The RCM, SHG, and TPF signal intensities of the treatment areas changed after high power femtosecond laser irradiation. The intensities of the RCM and SHG signals decreased when the tissue was damaged, while the intensity of the TPF signal increased when the photothermolysis was achieved. Moreover, the TPF signal was more susceptible to the degree of the photothermolysis than the RCM and SHG signals. The results suggested that multimodal microscopy is a potentially useful tool to monitor and assess the femtosecond laser treatment of the skin to achieve microscopic photothermolysis with high precision.

The role of multisensory interplay in enabling temporal expectations.

PubMed

Ball, Felix; Michels, Lara E; Thiele, Carsten; Noesselt, Toemme

2018-01-01

Temporal regularities can guide our attention to focus on a particular moment in time and to be especially vigilant just then. Previous research provided evidence for the influence of temporal expectation on perceptual processing in unisensory auditory, visual, and tactile contexts. However, in real life we are often exposed to a complex and continuous stream of multisensory events. Here we tested - in a series of experiments - whether temporal expectations can enhance perception in multisensory contexts and whether this enhancement differs from enhancements in unisensory contexts. Our discrimination paradigm contained near-threshold targets (subject-specific 75% discrimination accuracy) embedded in a sequence of distractors. The likelihood of target occurrence (early or late) was manipulated block-wise. Furthermore, we tested whether spatial and modality-specific target uncertainty (i.e. predictable vs. unpredictable target position or modality) would affect temporal expectation (TE) measured with perceptual sensitivity (d ' ) and response times (RT). In all our experiments, hidden temporal regularities improved performance for expected multisensory targets. Moreover, multisensory performance was unaffected by spatial and modality-specific uncertainty, whereas unisensory TE effects on d ' but not RT were modulated by spatial and modality-specific uncertainty. Additionally, the size of the temporal expectation effect, i.e. the increase in perceptual sensitivity and decrease of RT, scaled linearly with the likelihood of expected targets. Finally, temporal expectation effects were unaffected by varying target position within the stream. Together, our results strongly suggest that participants quickly adapt to novel temporal contexts, that they benefit from multisensory (relative to unisensory) stimulation and that multisensory benefits are maximal if the stimulus-driven uncertainty is highest. We propose that enhanced informational content (i.e. multisensory stimulation) enables the robust extraction of temporal regularities which in turn boost (uni-)sensory representations. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined modality treatment of aromatherapy, footsoak, and reflexology relieves fatigue in patients with cancer.

PubMed

Kohara, Hiroyuki; Miyauchi, Takako; Suehiro, Yoko; Ueoka, Hiroshi; Takeyama, Hiroyasu; Morita, Tatsuya

2004-12-01

Fatigue is one of the most distressful symptoms experienced by patients with advanced cancer. Aromatherapy, footsoak, and reflexology are popular health care modality treatments in Japan, however, the effectiveness of each treatment for cancer-related fatigue has not been fully established. To investigate the effectiveness of combined modality treatment consisting of aromatherapy, footsoak, and reflexology against fatigue, an open study was performed in 20 terminally ill patients with cancer. After a patch test was performed, patients received aromatherapy that was accompanied with footsoak in warm water containing lavender essential oil for 3 minutes, followed by reflexology treatment with jojoba oil containing lavender for 10 min. Fatigue was evaluated using the Cancer Fatigue Scale (CFS) before, 1 hour after, and 4 hours after treatment. Total CFS scores improved significantly after this treatment (from 25.6 +/- 11.0 to 18.1 +/- 10.0, p < 0.001). Among three CFS subscales, physical and cognitive subscale scores were reduced significantly (11.3 +/- 6.1 to 6.7 +/- 6.1, p < 0.001; 4.5 +/- 3.2 to 2.4 +/- 2.4, p < 0.001). No adverse effects were experienced. Because all patients desired to continue this treatment, they received treatment eight times on average. Combined modality treatment consisting of aromatherapy, footsoak, and reflexology appears to be effective for alleviating fatigue in terminally ill cancer patients. To confirm safety and effectiveness of this combined modality treatment, further investigation including randomized treatment assignment is warranted.

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

PubMed

Mohapatra, Shyam S; Batra, Surinder K; Bharadwaj, Srinivas; Bouvet, Michael; Cosman, Bard; Goel, Ajay; Jogunoori, Wilma; Kelley, Michael J; Mishra, Lopa; Mishra, Bibhuti; Mohapatra, Subhra; Patel, Bhaumik; Pisegna, Joseph R; Raufman, Jean-Pierre; Rao, Shuyun; Roy, Hemant; Scheuner, Maren; Singh, Satish; Vidyarthi, Gitanjali; White, Jon

2018-05-01

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

New approaches for identifying and testing potential new anti-asthma agents.

PubMed

Licari, Amelia; Castagnoli, Riccardo; Brambilla, Ilaria; Marseglia, Alessia; Tosca, Maria Angela; Marseglia, Gian Luigi; Ciprandi, Giorgio

2018-01-01

Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities. Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management. Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.

Opinions about Treatment Modalities among Patients Involuntarily Committed to a Forensic Psychiatric Hospital in Finland

ERIC Educational Resources Information Center

Repo-Tiihonen, Eila; Vuorio, Osmo; Koivisto, Hanna; Paavola, Paula; Hakola, Panu

2004-01-01

Patient satisfaction studies concerning various treatment modalities are few among involuntary forensic psychiatric treatment. They indicate general satisfaction with medication, interactive treatment and occupational therapy but dissatisfaction with lack of privacy, insufficiently explained rules and inadequately explained reasons of seclusion.…

Monitoring tumor growth and treatment in small animals with magnetic resonance and optical tomographic imaging

NASA Astrophysics Data System (ADS)

Masciotti, J.; Provenzano, F.; Papa, J.; Klose, A.; Hur, J.; Gu, X.; Yamashiro, D.; Kandel, J.; Hielscher, A. H.

2006-02-01

Small animal models are employed to simulate disease in humans and to study its progression, what factors are important to the disease process, and to study the disease treatment. Biomedical imaging modalities such as magnetic resonance imaging (MRI) and Optical Tomography make it possible to non-invasively monitor the progression of diseases in living small animals and study the efficacy of drugs and treatment protocols. MRI is an established imaging modality capable of obtaining high resolution anatomical images and along with contrast agents allow the studying of blood volume. Optical tomography, on the other hand, is an emerging imaging modality, which, while much lower in spatial resolution, can separate the effects of oxyhemoglobin, deoxyhemoglobin, and blood volume with high temporal resolution. In this study we apply these modalities to imaging the growth of kidney tumors and then there treatment by an anti-VEGF agent. We illustrate how these imaging modalities have their individual uses, but can still supplement each other and cross validation can be performed.

Oxygen beams for therapy: advanced biological treatment planning and experimental verification

NASA Astrophysics Data System (ADS)

Sokol, O.; Scifoni, E.; Tinganelli, W.; Kraft-Weyrather, W.; Wiedemann, J.; Maier, A.; Boscolo, D.; Friedrich, T.; Brons, S.; Durante, M.; Krämer, M.

2017-10-01

Nowadays there is a rising interest towards exploiting new therapeutical beams beyond carbon ions and protons. In particular, 16 O ions are being widely discussed due to their increased LET distribution. In this contribution, we report on the first experimental verification of biologically optimized treatment plans, accounting for different biological effects, generated with the TRiP98 planning system with 16 O beams, performed at HIT and GSI. This implies the measurements of 3D profiles of absorbed dose as well as several biological measurements. The latter includes the measurements of relative biological effectiveness along the range of linear energy transfer values from  ≈20 up to  ≈750 keV μ m-1 , oxygen enhancement ratio values and the verification of the kill-painting approach, to overcome hypoxia, with a phantom imitating an unevenly oxygenated target. With the present implementation, our treatment planning system is able to perform a comparative analysis of different ions, according to any given condition of the target. For the particular cases of low target oxygenation, 16 O ions demonstrate a higher peak-to-entrance dose ratio for the same cell killing in the target region compared to 12 C ions. Based on this phenomenon, we performed a short computational analysis to reveal the potential range of treatment plans, where 16 O can benefit over lighter modalities. It emerges that for more hypoxic target regions (partial oxygen pressure of  ≈0.15% or lower) and relatively low doses (≈4 Gy or lower) the choice of 16 O over 12 C or 4 He may be justified.

Recruitment and treatment practices for help-seeking "prodromal" patients.

PubMed

McGlashan, Thomas H; Addington, Jean; Cannon, Tyrone; Heinimaa, Markus; McGorry, Patrick; O'Brien, Mary; Penn, David; Perkins, Diana; Salokangas, Raimo K R; Walsh, Barbara; Woods, Scott W; Yung, Alison

2007-05-01

The prodrome of psychosis has become a target for early identification and for treatments that address both symptoms and risk for future psychosis. Interest and activity in this realm is now worldwide. Clinical trials with rigorous methodology have only just begun, making treatment guidelines premature. Despite the sparse evidence base, treatments are currently applied to patients in the new prodromal clinics, usually treatments developed for established psychosis and modified for the prodromal phase. This communication will describe representative samplings of how treatment-seeking prodromal patients are currently recruited and treated in prodromal clinics worldwide. Recruitment includes how prodromal patients are sought, initially evaluated, apprised of their high-risk status, and informed of the risks and benefits of prodromal treatments and how their mental state is monitored over time. The treatment modalities offered (and described) include engagement, supportive therapy, case management, stress management, cognitive behavioral treatment, family-based treatment, antipsychotic pharmacotherapy, and non-antipsychotic pharmacotherapy. References for details are noted.

Properties of intermodal transfer after dual visuo- and auditory-motor adaptation.

PubMed

Schmitz, Gerd; Bock, Otmar L

2017-10-01

Previous work documented that sensorimotor adaptation transfers between sensory modalities: When subjects adapt with one arm to a visuomotor distortion while responding to visual targets, they also appear to be adapted when they are subsequently tested with auditory targets. Vice versa, when they adapt to an auditory-motor distortion while pointing to auditory targets, they appear to be adapted when they are subsequently tested with visual targets. Therefore, it was concluded that visuomotor as well as auditory-motor adaptation use the same adaptation mechanism. Furthermore, it has been proposed that sensory information from the trained modality is weighted larger than sensory information from an untrained one, because transfer between sensory modalities is incomplete. The present study tested these hypotheses for dual arm adaptation. One arm adapted to an auditory-motor distortion and the other either to an opposite directed auditory-motor or visuomotor distortion. We found that both arms adapted significantly. However, compared to reference data on single arm adaptation, adaptation in the dominant arm was reduced indicating interference from the non-dominant to the dominant arm. We further found that arm-specific aftereffects of adaptation, which reflect recalibration of sensorimotor transformation rules, were stronger or equally strong when targets were presented in the previously adapted compared to the non-adapted sensory modality, even when one arm adapted visually and the other auditorily. The findings are discussed with respect to a recently published schematic model on sensorimotor adaptation. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

PubMed

Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

2015-07-01

Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The Potential of Nano-Vehicle Mediated Therapy in Vasculitis and Multiple Sclerosis.

PubMed

In't Veld, R Huis; Da Silva, C G; Kaijzel, E L; Chan, A B; Cruz, L J

2017-01-01

The induction of immune tolerance towards self-antigens presents as a viable future strategy in the treatment of auto-immune diseases, including vasculitis and multiple sclerosis (MS). As specific targets are currently lacking for vasculitis due to incomplete understanding of the pathologies underlying this disease, current treatment options are based on modalities that induce general immune suppression. However, many immune suppressants used in the clinic are known to display wide biodistribution and are thus often accompanied by several adverse effects. Nano-vehicles (NVs) possess the ability to overcome such limitations by enabling more specific delivery of their content through modifications with targeting moieties. In this review, we describe the latest insights in the pathology of vasculitis that may function as potential targets for NV carrier systems, allowing more specific delivery of currently used immune suppressants. In addition, we describe the existing strategies to induce artificial immune tolerance and explore the feasibility of inducing regulatory T cell (Treg) mediated tolerance for MS, possibly mediated by NVs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Immune checkpoint inhibitors for nonsmall cell lung cancer treatment.

PubMed

Chen, Yuh-Min

2017-01-01

Immune checkpoint inhibition with blocking antibodies that target cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the programmed cell death protein 1 (PD-1) pathway [PD-1/programmed death-ligand 1 (PD-L1)] have demonstrated promise in a variety of malignancies. While ipilimumab has been approved as a CTLA-4 blocking antibody by the US Food and Drug Administration for the treatment of advanced melanoma, it is still not approved for lung cancer treatment. In contrast, nivolumab and pembrolizumab, both PD-1 blocking antibodies, have been approved for second-line treatment of nonsmall cell lung cancer in 2015 because of their high potency and long-lasting effects in some patient subgroups. Other PD-1 and PD-L1 monoclonal antibodies are also in active development phase. Treatment with such immune checkpoint inhibitors is associated with a unique pattern of immune-related adverse events or side effects. Combination approaches involving CTLA-4 and PD-1/PD-L1 blockade or checkpoint inhibitors with chemotherapy or radiotherapy are being investigated to determine whether they may enhance the efficacy of treatment. Despite many challenges ahead, immunotherapy with checkpoint inhibitors has already become a new and important treatment modality for lung cancer in the last decade following the discovery of targeted therapy. Copyright © 2016. Published by Elsevier Taiwan LLC.

Prospects in the Application of Photodynamic Therapy in Oral Cancer and Premalignant Lesions

PubMed Central

Saini, Rajan; Lee, Nathan V.; Liu, Kelly Y. P.; Poh, Catherine F.

2016-01-01

Oral cancer is a global health burden with significantly poor survival, especially when the diagnosis is at its late stage. Despite advances in current treatment modalities, there has been minimal improvement in survival rates over the last five decades. The development of local recurrence, regional failure, and the formation of second primary tumors accounts for this poor outcome. For survivors, cosmetic and functional compromises resulting from treatment are often devastating. These statistics underscore the need for novel approaches in the management of this deadly disease. Photodynamic therapy (PDT) is a treatment modality that involves administration of a light-sensitive drug, known as a photosensitizer, followed by light irradiation of an appropriate wavelength that corresponds to an absorbance band of the sensitizer. In the presence of tissue oxygen, cytotoxic free radicals that are produced cause direct tumor cell death, damage to the microvasculature, and induction of inflammatory reactions at the target sites. PDT offers a prospective new approach in controlling this disease at its various stages either as a stand-alone therapy for early lesions or as an adjuvant therapy for advanced cases. In this review, we aim to explore the applications of PDT in oral cancer therapy and to present an overview of the recent advances in PDT that can potentially reposition its utility for oral cancer treatment. PMID:27598202

Treatment plan comparison of linac step and shoot, tomotherapy, rapidarc, and proton therapy for prostate cancer by using the dosimetrical and the biological indices

NASA Astrophysics Data System (ADS)

Lee, Suk; Cao, Yuan Jie; Chang, Kyung Hwan; Shim, Jang Bo; Kim, Kwang Hyeon; Lee, Nam Kwon; Park, Young Je; Kim, Chul Yong; Cho, Sam Ju; Lee, Sang Hoon; Min, Chul Kee; Kim, Woo Chul; Cho, Kwang Hwan; Huh, Hyun Do; Lim, Sangwook; Shin, Dongho

2015-07-01

The purpose of this study was to use various dosimetrical indices to determine the best intensitymodulated radiation therapy (IMRT) modality - for treating patients with prostate cancer. Ten patients with prostate cancer were included in this study. IMRT plans were designed to include different modalities, including the linac step and shoot, tomotherapy, RapidArc, and proton systems. Various dosimetrical indices, like the prescription isodose to target volume (PITV) ratio, conformity index (CI), homogeneity index (HI), target coverage index (TCI), modified dose homogeneity index (MHI), conformation number (CN), critical organ scoring index (COSI), and quality factor (QF), were determined to compare the different treatment plans. Biological indices, such as the generalized equivalent uniform dose (gEUD) based the tumor control probability (TCP), and the normal tissue complication probability (NTCP), were also calculated and used to compare the treatment plans. The RapidArc plan attained better PTV coverage, as evidenced by its superior PITV, CI, TCI, MHI, and CN values. Regarding organ at risks (OARs), proton therapy exhibited superior dose sparing for the rectum and the bowel in low dose volumes, whereas the tomotherapy and RapidArc plans achieved better dose sparing in high dose volumes. The QF scores showed no significant difference among these plans (p = 0.701). The average TCPs for prostate tumors in the RapidArc, linac and proton plans were higher than the average TCP for Tomotherapy (98.79%, 98.76%, and 98.75% vs. 98.70%, respectively). Regarding the rectum NTCP, RapidArc showed the most favorable result (0.09%) whereas linac resulted in the best bladder NTCP (0.08%).

Current Therapeutic Approach to Hypertrophic Scars

PubMed Central

Mokos, Zrinka Bukvić; Jović, Anamaria; Grgurević, Lovorka; Dumić-Čule, Ivo; Kostović, Krešimir; Čeović, Romana; Marinović, Branka

2017-01-01

Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome. PMID:28676850

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

Implications of Tumor Heterogeneity for Precision Medicine

NASA Astrophysics Data System (ADS)

Jeraj, Robert

Medical physics is intimately connected with medicine, and is progressing along a similar path. General trend of medicine, particularly oncology, towards personalized treatment gave rise to precision medicine, which addresses the highly complex nature of disease. However, there are severe obstacles to overcome. For example, cancers evolve in time to become harder targets to treat. Understanding treatment resistance, and its development, often connected with the highly heterogeneous nature of the disease, is another key obstacle. Use of multi-modality imaging techniques such as molecular imaging is one of the solutions that medical physics can offer. Examples from clinical trials utilizing advanced molecular imaging, highlighting intra-tumor and inter-tumor heterogeneity will be presented. New understanding of cancer treatment response dynamics will be outlined. Potential for improved patient treatment designs steaming from these novel insights will be discussed.

Brain metastases in women with epithelial ovarian cancer: multimodal treatment including surgery or gamma-knife radiation is associated with prolonged survival.

PubMed

Niu, Xiaoyu; Rajanbabu, Anupama; Delisle, Megan; Peng, Feng; Vijaykumar, Dehannathuparambil K; Pavithran, Keechilattu; Feng, Yukuan; Lau, Susie; Gotlieb, Walter H; Press, Joshua Z

2013-09-01

To explore the impact of treatment modality on survival in patients with brain metastases from epithelial ovarian cancer. We conducted a retrospective review of cases of ovarian cancer with brain metastases treated at institutions in three countries (Canada, China, and India) and conducted a search for studies regarding brain metastases in ovarian cancer reporting survival related to treatment modality. Survival was analyzed according to treatment regimens involving (1) some form of surgical excision or gamma-knife radiation with or without other modalities, (2) other modalities without surgery or gamma-knife radiation, or (3) palliation only. Twelve patients (mean age 56 years) with detailed treatment/outcome data were included; five were from China, four from Canada, and three from India. Median time from diagnosis of ovarian cancer to brain metastasis was 19 months (range 10 to 37 months), and overall median survival time from diagnosis of ovarian cancer was 38 months (13 to 82 months). Median survival time from diagnosis of brain metastasis was 17 months (1 to 45 months). Among patients who had multimodal treatment including gamma-knife radiotherapy or surgical excision, the median survival time after the identification of brain metastasis was 25.6 months, compared with 6.0 months in patients whose treatment did not include this type of focused localized modality (P = 0.006). Analysis of 20 studies also indicated that use of gamma-knife radiotherapy and excisional surgery in multi-modal treatment resulted in improved median survival interval (25 months vs. 6.0 months, P < 0.001). In the subset of patients with brain metastases from ovarian cancer, prolonged survival may result from use of multidisciplinary therapy, particularly if metastases are amenable to localized treatments such as gamma-knife radiotherapy and surgical excision.

Combined magnetic resonance imaging and ultrasound echography guidance for motion compensated HIFU interventions

NASA Astrophysics Data System (ADS)

Ries, Mario; de Senneville, Baudouin Denis; Regard, Yvan; Moonen, Chrit

2012-11-01

The objective of this study is to evaluate the feasibility to integrate ultrasound echography as an additional imaging modality for continuous target tracking, while performing simultaneously real-time MR- thermometry to guide a High Intensity Focused Ultrasound (HIFU) ablation. Experiments on a moving phantom were performed with MRI-guided HIFU during continuous ultrasound echography. Real-time US echography-based target tracking during MR-guided HIFU heating was performed with heated area dimensions similar to those obtained for a static target. The combination of both imaging modalities shows great potential for real-time beam steering and MR-thermometry.

Trojan horse at cellular level for tumor gene therapies.

PubMed

Collet, Guillaume; Grillon, Catherine; Nadim, Mahdi; Kieda, Claudine

2013-08-10

Among innovative strategies developed for cancer treatments, gene therapies stand of great interest despite their well-known limitations in targeting, delivery, toxicity or stability. The success of any given gene-therapy is highly dependent on the carrier efficiency. New approaches are often revisiting the mythic trojan horse concept to carry therapeutic nucleic acid, i.e. DNAs, RNAs or small interfering RNAs, to pathologic tumor site. Recent investigations are focusing on engineering carrying modalities to overtake the above limitations bringing new promise to cancer patients. This review describes recent advances and perspectives for gene therapies devoted to tumor treatment, taking advantage of available knowledge in biotechnology and medicine. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhancing the Delivery of an Empirically-Supported Trauma-Focused Treatment for Adolescents: Providers' Views of the Role of Technology and Web-Based Resources.

PubMed

Orengo-Aguayo, Rosaura E; Hanson, Rochelle F; Moreland, Angela D; Jobe-Shields, Lisa; Adams, Zachary W

2018-07-01

This mixed-methods study assessed providers' views of the use of technology in the delivery of an empirically supported mental health treatment for adolescents (Trauma-Focused Cognitive Behavioral Therapy; TF-CBT). Thematic qualitative interviews were conducted with nine experienced providers. Emerging themes served as the basis for the creation of a quantitative web-based survey, completed by 56 TF-CBT experts, to assess the perceived helpfulness of the recommendations. Technology was perceived as a useful, appealing, and familiar tool that could greatly enhance the delivery of this treatment modality with adolescents. Main recommendations included the creation of a mobile application targeting all of the treatment components and a website with developmentally appropriate resources for providers, caregivers, and teens. Technology may be a useful tool for enhancing service delivery and promoting engagement among youth receiving trauma-focused mental health treatment.

Long-Acting Antiretrovirals: Where Are We now?

PubMed

Nyaku, Amesika N; Kelly, Sean G; Taiwo, Babafemi O

2017-04-01

Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations. Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.

Ductal Carcinoma in Situ: Clinical Perspective.

PubMed

Kühn, Thorsten

2010-08-01

Ductal carcinoma is situ (DCIS) is the fastest growing subtype of breast cancer, mainly because of improved screening activities. In contrast to invasive disease, DCIS is a local process with excellent survival rates. Current treatment strategies include surgery, radiotherapy (RT) and anti-hormonal treatment. The selection of an individual risk-adapted therapeutic approach remains controversial. This relates especially to the extent of surgery and the therapeutic index of adjuvant RT and tamoxifen. Several new trials have been published or updated recently that address important clinical issues. There is an urgent need to get more insight into the biological behaviour of different subtypes of DCIS, and develop more targeted and individualized treatment strategies. So far, surgery appears to be the most effective treatment modality. A morphology-based treatment model that allows complete resection of certain DCIS lesions without further adjuvant measures has not been evaluated prospectively and deserves further evaluation.

Antisense technology: an emerging platform for cardiovascular disease therapeutics.

PubMed

Lee, Richard G; Crosby, Jeff; Baker, Brenda F; Graham, Mark J; Crooke, Rosanne M

2013-12-01

Antisense oligonucleotides and small interfering RNAs, which suppress the translation of specific mRNA target proteins, are emerging as important therapeutic modalities for the treatment of cardiovascular disease. Over the last 25 years, the advances in all aspects of antisense technology, as well as a detailed understanding of the mechanism of action of antisense drugs, have enabled their use as therapeutic agents. These advancements culminated in the FDA approval of the first chronically administered cardiovascular antisense therapeutic, mipomersen, which targets hepatic apolipoprotein B mRNA. This review provides a brief history of antisense technology, highlights the progression of mipomersen from preclinical studies to multiple Phase III registration trials, and gives an update on the status of other cardiovascular antisense therapeutics currently in the clinic.

At the Bench: Chimeric antigen receptor (CAR) T cell therapy for the treatment of B cell malignancies.

PubMed

Daniyan, Anthony F O; Brentjens, Renier J

2016-12-01

The chimeric antigen receptor (CAR) represents the epitome of cellular engineering and is one of the best examples of rational biologic design of a synthetic molecule. The CAR is a single polypeptide with modular domains, consisting of an antibody-derived targeting moiety, fused in line with T cell-derived signaling domains, allowing for T cell activation upon ligand binding. T cells expressing a CAR are able to eradicate selectively antigen-expressing tumor cells in a MHC-independent fashion. CD19, a tumor-associated antigen (TAA) present on normal B cells, as well as most B cell-derived malignancies, was an early target of this technology. Through years of experimental refinement and preclinical optimization, autologously derived CD19-targeting CAR T cells have been successfully, clinically deployed, resulting in dramatic and durable antitumor responses but not without therapy-associated toxicity. As CD19-targeted CAR T cells continue to show clinical success, work at the bench continues to be undertaken to increase further the efficacy of this therapy, while simultaneously minimizing the risk for treatment-related morbidities. In this review, we cover the history and evolution of CAR technology and its adaptation to targeting CD19. Furthermore, we discuss the future of CAR T cell therapy and the need to ask, as well as answer, critical questions as this treatment modality is being translated to the clinic. © Society for Leukocyte Biology.

A patient-specific computational model of hypoxia-modulated radiation resistance in glioblastoma using 18F-FMISO-PET

PubMed Central

Rockne, Russell C.; Trister, Andrew D.; Jacobs, Joshua; Hawkins-Daarud, Andrea J.; Neal, Maxwell L.; Hendrickson, Kristi; Mrugala, Maciej M.; Rockhill, Jason K.; Kinahan, Paul; Krohn, Kenneth A.; Swanson, Kristin R.

2015-01-01

Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient's disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [18F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning. PMID:25540239

Treatment of Pediculosis Capitis

PubMed Central

Verma, Prashant; Namdeo, Chaitanya

2015-01-01

An endeavour to delineate the salient details of the treatment of head lice infestation has been made in the present article. Treatment modalities including over the counter permethrin and pyrethrin, and prescription medicines, including malathion, lindane, benzyl alcohol, spinosad are discussed. Salient features of alternative medicine and physical treatment modalities are outlined. The problem of resistance to treatment has also been taken cognizance of. PMID:26120148

Immunotherapy of Human Papilloma Virus Induced Disease

PubMed Central

van der Burg, Sjoerd H

2012-01-01

Immunotherapy is the generic name for treatment modalities aiming to reinforce the immune system against diseases in which the immune system plays a role. The design of an optimal immunotherapeutic treatment against chronic viruses and associated diseases requires a detailed understanding of the interactions between the target virus and its host, in order to define the specific strategies that may have the best chance to deliver success at each stage of disease. Recently, a first series of successes was reported for the immunotherapy of Human Papilloma Virus (HPV)-induced premalignant diseases but there is definitely room for improvement. Here I discuss a number of topics that in my opinion require more study as the answers to these questions allows us to better understand the underlying mechanisms of disease and as such to tailor treatment. PMID:23341861

Surgical management of patients with primary brain tumors.

PubMed

Bohan, Eileen; Glass-Macenka, Deanna

2004-11-01

To provide an overview of the diagnostic work-up, intraoperative technologies, postoperative treatment options, and investigational new therapies in patients with malignant brain tumors. Published textbooks and articles and other reference materials. Recent improvements in diagnostic and surgical equipment have influenced outcomes and overall quality of life for patients with central nervous system tumors. The ability to more accurately target and more safely remove brain tumors has enhanced the postoperative period and decreased hospital stays. However, malignant neoplasms continue to be refractory to current treatments, necessitating innovative surgical approaches at the time of initial diagnosis and at tumor recurrence. Nurses with an understanding of current diagnostic and surgical treatment modalities for brain tumors are able to provide accurate patient education and comprehensive care, enhancing the overall hospital and outpatient experience.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

PubMed Central

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model.

PubMed

Singh, Amit; Xu, Jing; Mattheolabakis, George; Amiji, Mansoor

2016-04-01

In this study, we have formulated redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a targeted vector for systemic delivery of gemcitabine therapy in pancreatic cancer. The gelatin nanoparticles were formed by ethanol-induced desolvation process to encapsulate the bound drug. The surface of the nanoparticles was decorated either with poly(ethylene glycol) (PEG) chains to impart enhanced circulation time or with EGFR targeting peptide to confer target specificity. Our in vitro studies in Panc-1 human pancreatic ductal adenocarcinoma cells confirm that gemcitabine encapsulated in EGFR-targeted gelatin nanoparticles, released through disulfide bond cleavage, had a significantly improved cytotoxic profile. Further, the in vivo anticancer activity was evaluated in an orthotopic pancreatic adenocarcinoma tumor bearing SCID beige mice, which confirmed that EGFR-targeted gelatin nanoparticles could efficiently deliver gemcitabine to the tumor leading to higher therapeutic benefit as compared to the drug in solution. The treatment of pancreatic cancer remains unsatisfactory, with an average 5-year survival of less than 5%. New treatment modalities are thus urgently needed. In this study, the authors presented their formulation of redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a carrier for gemcitabine. In-vitro and in-vivo experiments showed encouraging results. It is hoped that the findings would provide a novel and alternative drug delivery platform for the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Unintended Embodiment of Concepts into Percepts: Sensory Activation Boosts Attention for Same-Modality Concepts in the Attentional Blink Paradigm

ERIC Educational Resources Information Center

Vermeulen, Nicolas; Mermillod, Martial; Godefroid, Jimmy; Corneille, Olivier

2009-01-01

This study shows that sensory priming facilitates reports of same-modality concepts in an attentional blink paradigm. Participants had to detect and report two target words (T1 and T2) presented for 53 ms each among a series of nonwords distractors at a frequency of up to 19 items per second. SOA between target words was set to 53 ms or 213 ms,…

The effect of unimodal affective priming on dichotic emotion recognition.

PubMed

Voyer, Daniel; Myles, Daniel

2017-11-15

The present report concerns two experiments extending to unimodal priming the cross-modal priming effects observed with auditory emotions by Harding and Voyer [(2016). Laterality effects in cross-modal affective priming. Laterality: Asymmetries of Body, Brain and Cognition, 21, 585-605]. Experiment 1 used binaural targets to establish the presence of the priming effect and Experiment 2 used dichotically presented targets to examine auditory asymmetries. In Experiment 1, 82 university students completed a task in which binaural targets consisting of one of 4 English words inflected in one of 4 emotional tones were preceded by binaural primes consisting of one of 4 Mandarin words pronounced in the same (congruent) or different (incongruent) emotional tones. Trials where the prime emotion was congruent with the target emotion showed faster responses and higher accuracy in identifying the target emotion. In Experiment 2, 60 undergraduate students participated and the target was presented dichotically instead of binaurally. Primes congruent with the left ear produced a large left ear advantage, whereas right congruent primes produced a right ear advantage. These results indicate that unimodal priming produces stronger effects than those observed under cross-modal priming. The findings suggest that priming should likely be considered a strong top-down influence on laterality effects.

IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

DTIC Science & Technology

2016-04-01

Hypomagnesemia, Grade 3 in 1 patient • Hypokalemia, Grade 3 in 2 patient • Pneumonia , Grade 3 in 7 patients • Dehydration, Grade 3 in 3 patients. Once...improvements on lab- scale radiosynthesis (Fig. 9) so that it is readily scaled up and adopted by the cGMP manufacturing. We are working on an automated...reproducibly building at the nanometer scale , including the need for streamlined and “bottom-up” approaches for assembling nanoparticle architectures, the

New Immunotherapy Strategies in Breast Cancer

PubMed Central

Yu, Lin-Yu; Tang, Jie; Zhang, Cong-Min; Zeng, Wen-Jing; Yan, Han; Li, Mu-Peng; Chen, Xiao-Ping

2017-01-01

Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies. PMID:28085094

Molecular image-directed biopsies: improving clinical biopsy selection in patients with multiple tumors

NASA Astrophysics Data System (ADS)

Harmon, Stephanie A.; Tuite, Michael J.; Jeraj, Robert

2016-10-01

Site selection for image-guided biopsies in patients with multiple lesions is typically based on clinical feasibility and physician preference. This study outlines the development of a selection algorithm that, in addition to clinical requirements, incorporates quantitative imaging data for automatic identification of candidate lesions for biopsy. The algorithm is designed to rank potential targets by maximizing a lesion-specific score, incorporating various criteria separated into two categories: (1) physician-feasibility category including physician-preferred lesion location and absolute volume scores, and (2) imaging-based category including various modality and application-specific metrics. This platform was benchmarked in two clinical scenarios, a pre-treatment setting and response-based setting using imaging from metastatic prostate cancer patients with high disease burden (multiple lesions) undergoing conventional treatment and receiving whole-body [18F]NaF PET/CT scans pre- and mid-treatment. Targeting of metastatic lesions was robust to different weighting ratios and candidacy for biopsy was physician confirmed. Lesion ranked as top targets for biopsy remained so for all patients in pre-treatment and post-treatment biopsy selection after sensitivity testing was completed for physician-biased or imaging-biased scenarios. After identifying candidates, biopsy feasibility was evaluated by a physician and confirmed for 90% (32/36) of high-ranking lesions, of which all top choices were confirmed. The remaining cases represented lesions with high anatomical difficulty for targeting, such as proximity to sciatic nerve. This newly developed selection method was successfully used to quantitatively identify candidate lesions for biopsies in patients with multiple lesions. In a prospective study, we were able to successfully plan, develop, and implement this technique for the selection of a pre-treatment biopsy location.

Economic evaluation of bone stimulation modalities: A systematic review of the literature.

PubMed

Button, Melissa L; Sprague, Sheila; Gharsaa, Osama; Latouche, Sandra; Bhandari, Mohit

2009-04-01

Various bone stimulation modalities are commonly used in treatment of fresh fractures and nonunions; however, the effectiveness and efficiency of these modalities remain uncertain. A systematic review of trials evaluating the clinical and economical outcomes of ultrasounds, electrical stimulation, and extracorporeal sound waves on fracture healing was conducted. We searched four electronic databases for economic evaluations that assessed bone stimulation modalities using ultrasound therapy, electrical stimulation, or extracorporeal shock waves. In addition, we searched the references and related articles of eligible studies, and a content expert was contacted. Information on the clinical and economical outcomes of patients was independently extracted by reviewers. Fourteen studies met the inclusion criteria; therefore, very limited research was found on the cost associated with treatments and the corresponding outcomes. The data available focus primarily on the efficacy of newly introduced treatment methods for bone growth, but failed to incorporate the costs of implementing such treatments. One economic analysis was identified that assessed different treatment paths using ultrasound. A total cost savings of 24-40% per patient occurred when ultrasound was used for fresh fractures and nonunions (grade C recommendation). The results suggest that the ultrasound is a viable alternative for bone stimulation; however, the impacts of the other modalities are left unknown due to the lack of research available. Methodological limitations leave the overall economic and clinical impact of these modalities uncertain. Large, prospective, randomized controlled trials that include cost-effectiveness analyses are needed to further define the clinical effectiveness and financial burden associated with bone stimulation modalities.

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

PubMed Central

Luo, Dandan; Carter, Kevin A.; Miranda, Dyego

2016-01-01

Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted. PMID:28105389

CARs and other T cell therapies for MM: The clinical experience.

PubMed

Danhof, Sophia; Hudecek, Michael; Smith, Eric L

2018-06-01

Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical investigation. Most recent clinical protocols have focused on targeting B-cell maturation antigen (BCMA), and early results are promising. The trials differ in receptor constructs, patient selection, dosing strategies and conditioning chemotherapy and will thus pave the way to eventually define the optimal parameters. Other sources for autologous T-cell therapy of MM include affinity-enhanced T-cell receptor-modified cells and marrow infiltrating lymphocytes. In summary, adoptive T-cell transfer for the treatment of MM is still in its infancy, but if early response rates indicate durability, will be a paradigm changing therapeutic modality for the treatment of MM. Copyright © 2018. Published by Elsevier Ltd.

Multimodal Approaches to Define Network Oscillations in Depression

PubMed Central

Smart, Otis Lkuwamy; Tiruvadi, Vineet Ravi; Mayberg, Helen S.

2018-01-01

The renaissance in the use of encephalography-based research methods to probe the pathophysiology of neuropsychiatric disorders is well afoot and continues to advance. Building on the platform of neuroimaging evidence on brain circuit models, magnetoencephalography, scalp electroencephalography, and even invasive electroencephalography are now being used to characterize brain network dysfunctions that underlie major depressive disorder using brain oscillation measurements and associated treatment responses. Such multiple encephalography modalities provide avenues to study pathologic network dynamics with high temporal resolution and over long time courses, opportunities to complement neuroimaging methods and findings, and new approaches to identify quantitative biomarkers that indicate critical targets for brain therapy. Such goals have been facilitated by the ongoing testing of novel invasive neuromodulation therapies, notably, deep brain stimulation, where clinically relevant treatment effects can be monitored at multiple brain sites in a time-locked causal manner. We review key brain rhythms identified in major depressive disorder as foundation for development of putative biomarkers for objectively evaluating neuromodulation success and for guiding deep brain stimulation or other target-based neuromodulation strategies for treatment-resistant depression patients. PMID:25681871

Improving external beam radiotherapy by combination with internal irradiation.

PubMed

Dietrich, A; Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

2015-07-01

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

Trismus following different treatment modalities for head and neck cancer: a systematic review of subjective measures.

PubMed

Loh, Sook Y; Mcleod, Robert W J; Elhassan, Hassan A

2017-07-01

The aim of this review was to compare systematically the subjective measure of trismus between different interventions to treat head and neck cancer, particularly those of the oropharynx. Using The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines, Six databases were searched for the text using various terms which include "oropharyngeal/head and neck cancer", "trismus/mouth opening" and the various treatment modalities. Included in the review were clinical studies (> or =10 patients). Three observers independently assessed the papers identified. Among the six studies reviewed, five showed a significantly worst outcome with regard to the quality-of-life questionnaire scores for a radiotherapy or surgery and radiotherapy (RT) ± chemotherapy or chemoradiotherapy when compared to surgery alone. Only one study showed no significant difference between surgery alone and other treatment modalities. Subjective quality-of-life measures are a concurrent part of modern surgical practice. Although subjective measures were utilised to measure post operative trismus successfully, there was no consensus as to which treatment modality had overall better outcomes, with conflicting studies in keeping with the current debate in this field. Larger and higher quality studies are needed to compare all three treatment modalities.

Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

PubMed Central

Ostrowski, Robert P.; Stępień, Katarzyna; Pucko, Emanuela; Matyja, Ewa

2016-01-01

The effectiveness and efficacy of hyperbaric oxygen (HBO) preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient focal ischemia may even aggravate brain injury. This review advocates the level of injury reduction upon HBO as an important component for translational evaluation of HBO based treatment modalities. The combined preconditioning and HBO post-treatment that would provide synergistic effects is also worth considering. PMID:27826422

Treatment modalities of palmoplantar lichen planus: a brief review.

PubMed

Feily, Amir; Yaghoobi, Reza; Nilforoushzadeh, Mohammad Ali

2016-12-01

Palmoplantar lichen planus is a localized and uncommon variant of lichen planus which is mostly resistant to treatment. Our purpose was to discuss all treatment modalities proposed and tested for palmoplantar lichen planus in the literature. A systematic review of the literature was conducted to evaluate evidence regarding all treatment modalities proposed and tested for palmoplantar lichen planus in the literature. Two major databases (PubMed, Google scholar) were searched. The review included all case reports, letters and original articles reporting any treatment for palmoplantar lichen planus but not treatment used in the other type of lichen planus, generalized lichen planus or other type of palmoplantar dermatoses. We have gone over more than 50 articles. There are many drugs that have been used in the treatment of lichen planus and generalized lichen planus but the palmoplantar type is a rare variety of lichen planus. That is why we could not find any clinical trial on the subject and just case reports have been described in this manuscript. In spite of plentiful investigations carried out on lichen planus, there is no treatment modality that has proved to be utterly satisfactory in treatment of palmoplantar lichen planus.

Online Multi-Modal Robust Non-Negative Dictionary Learning for Visual Tracking

PubMed Central

Zhang, Xiang; Guan, Naiyang; Tao, Dacheng; Qiu, Xiaogang; Luo, Zhigang

2015-01-01

Dictionary learning is a method of acquiring a collection of atoms for subsequent signal representation. Due to its excellent representation ability, dictionary learning has been widely applied in multimedia and computer vision. However, conventional dictionary learning algorithms fail to deal with multi-modal datasets. In this paper, we propose an online multi-modal robust non-negative dictionary learning (OMRNDL) algorithm to overcome this deficiency. Notably, OMRNDL casts visual tracking as a dictionary learning problem under the particle filter framework and captures the intrinsic knowledge about the target from multiple visual modalities, e.g., pixel intensity and texture information. To this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for each modality from available frames, and then represents new particles over all the learned dictionaries by minimizing the fitting loss of data based on M-estimation. The resultant representation coefficient can be viewed as the common semantic representation of particles across multiple modalities, and can be utilized to track the target. OMRNDL incrementally learns the dictionary and the coefficient of each particle by using multiplicative update rules to respectively guarantee their non-negativity constraints. Experimental results on a popular challenging video benchmark validate the effectiveness of OMRNDL for visual tracking in both quantity and quality. PMID:25961715

Online multi-modal robust non-negative dictionary learning for visual tracking.

PubMed

Zhang, Xiang; Guan, Naiyang; Tao, Dacheng; Qiu, Xiaogang; Luo, Zhigang

2015-01-01

Dictionary learning is a method of acquiring a collection of atoms for subsequent signal representation. Due to its excellent representation ability, dictionary learning has been widely applied in multimedia and computer vision. However, conventional dictionary learning algorithms fail to deal with multi-modal datasets. In this paper, we propose an online multi-modal robust non-negative dictionary learning (OMRNDL) algorithm to overcome this deficiency. Notably, OMRNDL casts visual tracking as a dictionary learning problem under the particle filter framework and captures the intrinsic knowledge about the target from multiple visual modalities, e.g., pixel intensity and texture information. To this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for each modality from available frames, and then represents new particles over all the learned dictionaries by minimizing the fitting loss of data based on M-estimation. The resultant representation coefficient can be viewed as the common semantic representation of particles across multiple modalities, and can be utilized to track the target. OMRNDL incrementally learns the dictionary and the coefficient of each particle by using multiplicative update rules to respectively guarantee their non-negativity constraints. Experimental results on a popular challenging video benchmark validate the effectiveness of OMRNDL for visual tracking in both quantity and quality.

Bacterial vaginosis: Etiology and modalities of treatment—A brief note

PubMed Central

Kumar, Nikhil; Behera, Beauty; Sagiri, Sai S.; Pal, Kunal; Ray, Sirsendu S.; Roy, Saroj

2011-01-01

A large women population of the world is suffering from a vaginal infection commonly known as bacterial vaginosis. The disease is associated with the decrease in the lactobacilli count in the vagina. Till date, there is a lack of full proof treatment modalities for the cure of the disease. The treatment includes the use of antimicrobials and/or acidifying agents and probiotics, either separately or in combination. This note discusses about the etiology and the various present-day modalities of treatment of bacterial vaginosis. PMID:22219582

Efficacy of a modern neuroscience approach versus usual care evidence-based physiotherapy on pain, disability and brain characteristics in chronic spinal pain patients: protocol of a randomized clinical trial

PubMed Central

2014-01-01

Background Among the multiple conservative modalities, physiotherapy is a commonly utilized treatment modality in managing chronic non-specific spinal pain. Despite the scientific progresses with regard to pain and motor control neuroscience, treatment of chronic spinal pain (CSP) often tends to stick to a peripheral biomechanical model, without targeting brain mechanisms. With a view to enhance clinical efficacy of existing physiotherapeutic treatments for CSP, the development of clinical strategies targeted at ‘training the brain’ is to be pursued. Promising proof-of-principle results have been reported for the effectiveness of a modern neuroscience approach to CSP when compared to usual care, but confirmation is required in a larger, multi-center trial with appropriate evidence-based control intervention and long-term follow-up. The aim of this study is to assess the effectiveness of a modern neuroscience approach, compared to usual care evidence-based physiotherapy, for reducing pain and improving functioning in patients with CSP. A secondary objective entails examining the effectiveness of the modern neuroscience approach versus usual care physiotherapy for normalizing brain gray matter in patients with CSP. Methods/Design The study is a multi-center, triple-blind, two-arm (1:1) randomized clinical trial with 1-year follow-up. 120 CSP patients will be randomly allocated to either the experimental (receiving pain neuroscience education followed by cognition-targeted motor control training) or the control group (receiving usual care physiotherapy), each comprising of 3 months treatment. The main outcome measures are pain (including symptoms and indices of central sensitization) and self-reported disability. Secondary outcome measures include brain gray matter structure, motor control, muscle properties, and psychosocial correlates. Clinical assessment and brain imaging will be performed at baseline, post-treatment and at 1-year follow-up. Web-based questionnaires will be completed at baseline, after the first 3 treatment sessions, post-treatment, and at 6 and 12-months follow-up. Discussion Findings may provide empirical evidence on: (1) the effectiveness of a modern neuroscience approach to CSP for reducing pain and improving functioning, (2) the effectiveness of a modern neuroscience approach for normalizing brain gray matter in CSP patients, and (3) factors associated with therapy success. Hence, this trial might contribute towards refining guidelines for good clinical practice and might be used as a basis for health authorities’ recommendations. Trial registration ClinicalTrials.gov Identifier: NCT02098005. PMID:24885889

Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

PubMed

Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

2012-02-01

The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings.

Concordance of IHC, FISH and RT-PCR for EML4-ALK rearrangements.

PubMed

Teixidó, Cristina; Karachaliou, Niki; Peg, Vicente; Gimenez-Capitan, Ana; Rosell, Rafael

2014-04-01

The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) has emerged as the second most important driver oncogene in lung cancer and the first targetable fusion oncokinase to be identified in 4-6% of lung adenocarcinomas. Crizotinib, along with a diagnostic test-the Vysis ALK Break Apart fluorescence in situ hybridization (FISH) Probe Kit-is approved for the treatment of ALK positive advanced non-small cell lung cancer (NSCLC). However, the success of a targeted drug is critically dependent on a sensitive and specific screening assay to detect the molecular drug target. In our experience, reverse transcription polymerase chain reaction (RT-PCR)-based detection of EML4-ALK is a more sensitive and reliable approach compared to FISH and immunohistochemistry (IHC). Although ALK FISH is clinically validated, the assay can be technically challenging and other diagnostic modalities, including IHC and RT-PCR should be further explored.

Molecular biology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

PubMed

Nana-Sinkam, Serge Patrick; Powell, Charles A

2013-05-01

Based on recent bench and clinical research, the treatment of lung cancer has been refined, with treatments allocated according to histology and specific molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors has been particularly successful as a treatment modality, demonstrating response rates in selected patients with adenocarcinoma tumors harboring EGFR mutations that are significantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, and the development of highly reproducible platforms for high-throughput biomarker discovery and testing. In this article, we review clinically relevant research directed toward understanding the biology of lung cancer. The clinical purposes of this research are (1) to identify susceptibility variants and field molecular alterations that will promote the early detection of tumors and (2) to identify tumor molecular alterations that serve as therapeutic targets, prognostic biomarkers, or predictors of tumor response. We focus on research developments in the understanding of lung cancer somatic DNA mutations, chromosomal aberrations, epigenetics, and the tumor microenvironment, and how they can advance diagnostics and therapeutics.

Novel therapies and their integration into allogeneic stem cell transplant for chronic lymphocytic leukemia.

PubMed

Jaglowski, Samantha M; Byrd, John C

2012-01-01

Over the past decade, numerous advances have been made in elucidating the biology of and improving treatment for chronic lymphocytic leukemia (CLL). These studies have led to identification of select CLL patient groups that generally have short survival dating from time of treatment or initial disease relapse who benefit from more aggressive therapeutic interventions. Allogeneic transplantation represents the only potentially curative option for CLL, but fully ablative regimens applied in the past have been associated with significant morbidity and mortality. Reduced-intensity preparative regimens has made application of allogeneic transplant to CLL patients much more feasible and increased the number of patients proceeding to this modality. Arising from this has been establishment of guidelines where allogeneic stem cell transplantation should be considered in CLL. Introduction of new targeted therapies with less morbidity, which can produce durable remissions has the potential to redefine where transplantation is initiated in CLL. This review briefly summarizes the field of allogeneic stem cell transplant in CLL and the interface of new therapeutics with this modality. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hydrogen Sulfide in Hypertension and Kidney Disease of Developmental Origins.

PubMed

Hsu, Chien-Ning; Tain, You-Lin

2018-05-11

Adverse environments occurring during kidney development may produce long-term programming effects, namely renal programming, to create increased vulnerability to the development of later-life hypertension and kidney disease. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life, even before the onset of clinical symptoms, which may counter the rising epidemic of hypertension and kidney disease. Hydrogen sulfide (H₂S), the third gasotransmitter, plays a key role in blood pressure regulation and renal physiology. This review will first present the role of H₂S in the renal system and provide evidence for the links between H₂S signaling and the underlying mechanisms of renal programming, including the renin⁻angiotensin system, oxidative stress, nutrient-sensing signals, sodium transporters, and epigenetic regulation. This will be followed by potential H₂S treatment modalities that may serve as reprogramming strategies to prevent hypertension and kidney disease of developmental origins. These H₂S treatment modalities include precursors for H₂S synthesis, H₂S donors, and natural plant-derived compounds. Despite emerging evidence from experimental studies in support of reprogramming strategies targeting the H₂S signaling pathway to protect against hypertension and kidney disease of developmental origins, these results need further clinical translation.

Radiofrequency ablation of hepatocellular carcinoma: pros and cons.

PubMed

Rhim, Hyunchul; Lim, Hyo K

2010-09-01

Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excellent local tumor control, 3) it has promising long-term survival, and 4) it is a multimodal approach. Based on these pros, RFA will play an important role in managing the patient with early HCC (smaller than 3 cm with fewer than four tumors). The main limitations of current RFA technology in hepatic ablation include 1) limitation of ablation volume, 2) technically infeasible in some tumors due to conspicuity and dangerous location, and 3) the heat-sink effect. Many technical approaches have been introduced to overcome those limitations, including a novel guiding modality, use of artificial fluid or air, and combined treatment strategies. RFA will continue to play a role as a representative ablative modality in the management of HCC, even in the era of targeted agents.

Radiofrequency Ablation of Hepatocellular Carcinoma: Pros and Cons

PubMed Central

Lim, Hyo K.

2010-01-01

Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excellent local tumor control, 3) it has promising long-term survival, and 4) it is a multimodal approach. Based on these pros, RFA will play an important role in managing the patient with early HCC (smaller than 3 cm with fewer than four tumors). The main limitations of current RFA technology in hepatic ablation include 1) limitation of ablation volume, 2) technically infeasible in some tumors due to conspicuity and dangerous location, and 3) the heat-sink effect. Many technical approaches have been introduced to overcome those limitations, including a novel guiding modality, use of artificial fluid or air, and combined treatment strategies. RFA will continue to play a role as a representative ablative modality in the management of HCC, even in the era of targeted agents. PMID:21103289

Tracking Organs Composed of One or Multiple Regions Using Geodesic Active Region Models

NASA Astrophysics Data System (ADS)

Martínez, A.; Jiménez, J. J.

In radiotherapy treatment it is very important to find out the target organs on the medical image sequence in order to determine and apply the proper dose. The techniques to achieve this goal can be classified into extrinsic and intrinsic. Intrinsic techniques only use image processing with medical images associated to the radiotherapy Radiotherapy treatment, as we deal in this chapter. To accurately perform this organ tracking it is necessary to find out segmentation and tracking models that were able to be applied to several image modalities involved on a radiotherapy session (CT CT See Modality , MRI Magnetic resoance imaging , etc.). The movements of the organs are mainly affected by two factors: breathing and involuntary movements associated with the internal organs or patient positioning. Among the several alternatives to track the organs of interest, a model based on geodesic active regions is proposed. This model has been tested over CT Computed tomography images from the pelvic, cardiac, and thoracic area. A new model for the segmentation of organs composed by more than one region is proposed.

Non-surgical treatments for the management of early osteoarthritis.

PubMed

Filardo, Giuseppe; Kon, Elizaveta; Longo, Umile Giuseppe; Madry, Henning; Marchettini, Paolo; Marmotti, Antonio; Van Assche, Dieter; Zanon, Giacomo; Peretti, Giuseppe M

2016-06-01

Non-surgical treatments are usually the first choice for the management of knee degeneration, especially in the early osteoarthritis (OA) phase when no clear lesions or combined abnormalities need to be addressed surgically. Early OA may be addressed by a wide range of non-surgical approaches, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as physical therapies and novel biological minimally invasive procedures involving injections of various substances to obtain a clinical improvement and possibly a disease-modifying effect. Numerous pharmaceutical agents are able to provide clinical benefit, but no one has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level. Patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. Among these, exercise is an effective conservative approach, while physical therapies lack literature support. Even though a combination of these therapeutic options might be the most suitable strategy, there is a paucity of studies focusing on combining treatments, which is the most common clinical scenario. Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early OA. In fact, most of the available evidence regards established OA. Increased knowledge about degeneration mechanisms will help to better target the available treatments and develop new biological options, where preliminary results are promising, especially concerning early disease phases. Specific treatments aimed at improving joint homoeostasis, or even counteracting tissue damage by inducing regenerative processes, might be successful in early OA, where tissue loss and anatomical changes are still at very initial stages.

Comparing the photothermal effects of gold nanorods and single-walled carbon nanotubes in cancer models

NASA Astrophysics Data System (ADS)

West, Connor L.; Hasanjee, Aamr M.; Young, Blake; Wolf, Roman; Silk, Kegan; Ingalls, Rianna; Zhou, Feifan; Chen, Wei R.

2017-02-01

Laser Immunotherapy (LIT) is an innovative cancer treatment modality that is specifically targeted towards treating late-stage, metastatic cancer. This treatment modality utilizes laser irradiation in combination with active immune system stimulation to induce a systemic anti-tumor immune response against metastatic cancer. Nanoparticles have recently been utilized to support and increase the photothermal effect of the laser irradiation by absorbing the light energy produced from the laser and converting that energy into thermal energy. In the past, single-walled carbon nanotubes (SWNTs) have been the main choice in nanotechnology, however, recent studies have shown that gold nanorods (AuNRs) are a prospective alternative that may produce photothermal effects similar to SWNTs. Due to the precedence of gold biomaterials currently having approval for use in various treatments for humans, AuNRs are regarded to be a safer option than SWNTs. The goal of this study is to precisely compare any differences in photothermal effects between AuNRs and SWNTs. Both types of nanoparticles were irradiated with the same wavelength of near-infrared light to ascertain the photothermal effects in gel phantom tumor models, aqueous solutions, and metastatic cancer cell cultures. We discerned from the results that the AuNRs could be equally or more effective than SWNTs in absorbing the light energy from the laser and converting it into thermal energy. In both solution and gel studies, AuNRs were shown to be more efficient than SWNTs in creating thermal energy, while in cell studies, no definitive differences between AuNRs and SWNTs were observed. The cytotoxicity of both nanoparticles needs further assessment in future studies. Given these results, AuNRs are comparable to SWNTs, even superior in certain aspects. This advances the opportunity to use AuNRs as replacements for SWNTs in LIT treatments. The results from this study will contribute to any subsequent studies in the development of this cancer modality using photothermal therapy enhanced by nanoparticles.

Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults.

PubMed

Lee, Ahreum; Ryu, Hokyoung; Kim, Jae-Kwan; Jeong, Eunju

2018-04-11

Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standar Desviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition.

The effect of the Xpert MTB/RIF test on the time to MDR-TB treatment initiation in a rural setting: a cohort study in South Africa's Eastern Cape Province.

PubMed

Iruedo, Joshua; O'Mahony, Don; Mabunda, Sikhumbuzo; Wright, Graham; Cawe, Busisiwe

2017-01-21

There are significant delays in initiation of multidrug-resistant tuberculosis (MDR -TB) treatment. The Xpert MTB/RIF test has been shown to reduce the time to diagnosis and treatment of MDR-TB predominantly in urban centres. This study describes the time to treatment of MDR-TB and the effect of Xpert MTB/RIF on time to treatment in a deprived rural area in South Africa. This was a retrospective cohort study analysing the medical records of patients diagnosed with MDR-TB in King Sabata Dalindyebo Sub-District between 2009 and 2014. Numerical data were reported using the Kruskal-Wallis and Wilcoxon sum rank tests and categorical data compared using the two-sample test of proportions. Of the 342 patients with MDR-TB identified, 285 were eligible for analysis, of whom 145 (61.4%) were HIV positive. The median time from sputum collection to MDR-TB diagnosis was 27 days (IQR: 2-45) and differed significantly between diagnostic modalities: Xpert MTB/RIF, 1 day (IQR: 1-4; n = 114: p < 0.0001); Line Probe Assay 12 days (IQR: 8-21; n = 28; p < 0.0001); and culture/phenotypic drug sensitivity testing 45 days (IQR: 39-59; n = 143: p < 0.0001). The time from diagnosis to treatment initiation was 14 days (IQR: 8-27) and did not differ significantly between diagnostic modality. The median time from sputum collection to treatment initiation was 49 days (IQR: 20-69) but differed significantly between diagnostic modalities: Xpert MTB/RIF, 18 days (IQR: 11-27; n = 114; p < 0.0001); Line Probe Assay 29 days (IQR: 14.5-53; n = 28; p < 0.0001); and culture/phenotypic drug sensitivity, 64 days (IQR: 50-103; n = 143: P < 0.0001). Age, sex and HIV status did not influence the time intervals. Xpert MTB/RIF significantly reduced the time to MDR-TB treatment in a deprived rural setting as a result of a reduced time to diagnosis. However, the national target of five days was not achieved. Further research is needed to explore and address programmatic and patient-related challenges contributing to delayed treatment initiation.

Targeting the neurophysiology of cognitive systems with transcranial alternating current stimulation (tACS)

PubMed Central

Fröhlich, Flavio; Sellers, Kristin K.; Cordle, Asa L.

2015-01-01

Cognitive impairment represents one of the most debilitating and most difficult symptom to treat of many psychiatric illnesses. Human neurophysiology studies have suggested specific pathologies of cortical network activity correlate with cognitive impairment. However, we lack (1) demonstration of causal relationships between specific network activity patterns and cognitive capabilities and (2) treatment modalities that directly target impaired network dynamics of cognition. Transcranial alternating current stimulation (tACS), a novel non-invasive brain stimulation approach, may provide a crucial tool to tackle these challenges. We here propose that tACS can be used to elucidate the causal role of cortical synchronization in cognition and, eventually, to enhance pathologically weakened synchrony that may underlie cognitive deficits. To accelerate such development of tACS as a treatment for cognitive deficits, we discuss studies on tACS and cognition (all performed in healthy participants) according to the Research Domain Criteria (RDoC) of the National Institute of Mental Health. PMID:25547149

Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT

NASA Astrophysics Data System (ADS)

Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba

2009-06-01

Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

PubMed Central

Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

2014-01-01

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2 + AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

Novel Non-invasive Treatment With High-intensity Focused Ultrasound (HIFU).

PubMed

Marinova, M; Rauch, M; Schild, H H; Strunk, H M

2016-02-01

Ultrasound is not only used for diagnostic purposes but it also can be applied therapeutically so far that nowadays high-intensity focused ultrasound (HIFU) even represents a novel non-invasive treatment modality for various solid tumors. HIFU works by causing selectively deep tissue destruction of target lesions within the body without harming adjacent and overlying structures. In this article, we present an overview on both the mode of action and requirements for a HIFU treatment as well as on the safety and the current status of indications and possible applications with regard to benign and malignant gynecological diseases. Based on numerous studies and original articles, HIFU proved to be an effective and low-risk treatment option particularly for uterine fibroids and adenomyosis, but it also seems to be effective for breast fibroadenomas or even for breast cancer in special cases and other rare entities. © Georg Thieme Verlag KG Stuttgart · New York.

Streptomycin-lidocaine injections for the treatment of postherpetic neuralgia: Report of three cases with literature review.

PubMed

Waghray, Shefali; Asif, Shaik Mohammed; Duddu, Mahesh Kumar; Arakeri, Gururaj

2013-09-01

The sudden, stabbing, paroxysmal pain of neuralgia is the fiercest agony that a patient may experience in his life. Many varied medical treatments and surgical procedures have been suggested in the literature for neuralgic pain. Most of the patients fail to respond to medical treatments or succumb to complications of total anesthesia owing to surgical procedures. Herein, we tried a new treatment modality in patients suffering from postherpetic neuralgia with appreciable success in all the three cases that are presented in this paper. Streptomycin sulfate dissolved in 2% lidocaine solution was deposited at the peripheral branches on the involved nerves targeting the trigger zones, given weekly once for a maximum of 6 week period and continued once in 2 weeks if symptoms persisted. All patients were followed-up for 1 year and there was a marked improvement on follow-up.

Streptomycin-lidocaine injections for the treatment of postherpetic neuralgia: Report of three cases with literature review

PubMed Central

Waghray, Shefali; Asif, Shaik Mohammed; Duddu, Mahesh Kumar; Arakeri, Gururaj

2013-01-01

The sudden, stabbing, paroxysmal pain of neuralgia is the fiercest agony that a patient may experience in his life. Many varied medical treatments and surgical procedures have been suggested in the literature for neuralgic pain. Most of the patients fail to respond to medical treatments or succumb to complications of total anesthesia owing to surgical procedures. Herein, we tried a new treatment modality in patients suffering from postherpetic neuralgia with appreciable success in all the three cases that are presented in this paper. Streptomycin sulfate dissolved in 2% lidocaine solution was deposited at the peripheral branches on the involved nerves targeting the trigger zones, given weekly once for a maximum of 6 week period and continued once in 2 weeks if symptoms persisted. All patients were followed-up for 1 year and there was a marked improvement on follow-up. PMID:24966716

Current and Under Development Treatment Modalities of Psoriasis: A Review.

PubMed

Albaghdadi, Abdullah

2017-01-01

Psoriasis is a chronic and complex autoimmune inflammatory skin disease that affects over 125 million people worldwide. It can exhibit at any age, in spite of the fact that children are less normally influenced than adults. It is characterized by distinct erythematous plaques shielded with conspicuous silvery scales that shows up in different areas of the skin. Knowledge of pathophysiology, especially the pathogenesis of psoriasis, has significantly progressed in the recent decade. Advancement in molecular knowledge leads to better understanding of the disease, thus influencing the development of efficient treatment modalities. However, even with the availability of various options of treatment most of the efficient treatment modalities are costly. Expenses of health care bring about major financial weight to the patients as well as to health care systems. Thus, it was important to review the available current treatment options and those which are under development, in terms of efficacy, safety and cost to assist in selecting the most appropriate treatment for psoriasis patients. Literatures were searched by using key words psoriasis, topical treatment, systemic treatment, biologics and phototherapies, on Embase, Medline, Jstor, Cochrane and Merck Index databases. Life-style choices such as smoking, alcohol consumption, obesity and stress are recognised as risk factors and triggers associated with psoriasis. Psoriasis poses psycho-social and economic burden on affected patients that sometimes leads to depression, reduced social interaction and suicidal tendencies in patients. Depending on the type, severity and extent of the disease, comorbidities, patient preference, efficacy and safety profile, numerous treatment modalities and therapeutic agents are available such as topical, systemic, biologic and phototherapeutic treatments. However, it was found that among all the current available treatments for psoriasis, biologic agents and phototherapeutic modalities are the most commonly employed treatment modalities for moderate to severe psoriasis. Evaluation of present-day available treatment alternatives will surely help physician to select a suitable module for each patient while keeping in mind the financial status of the patient. Future research should aim to develop therapies which are efficient, safe and cost-effective. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors

PubMed Central

Kuwahara, Yoshikazu; Mori, Miyuki; Kitahara, Shuji; Fukumoto, Motoi; Ezaki, Taichi; Mori, Shiro; Echigo, Seishi; Ohkubo, Yasuhito; Fukumoto, Manabu

2014-01-01

Radiotherapy is widely used to treat cancer because it has the advantage of physically and functionally conserving the affected organ. To improve radiotherapy and investigate the molecular mechanisms of cellular radioresistance, we established a clinically relevant radioresistant (CRR) cell line, SAS-R, from SAS cells. SAS-R cells continue to proliferate when exposed to fractionated radiation (FR) of 2 Gy/day for more than 30 days in vitro. A xenograft tumor model of SAS-R was also resistant to 2 Gy/day of X-rays for 30 days. The density of blood vessels in SAS-R tumors was higher than in SAS tumors. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, sensitized microvascular endothelial cells to radiation, but failed to radiosensitize SAS and SAS-R cells in vitro. Everolimus with FR markedly reduced SAS and SAS-R tumor volumes. Additionally, the apoptosis of endothelial cells (ECs) increased in SAS-R tumor tissues when both Everolimus and radiation were administered. Both CD34-positive and tomato lectin-positive blood vessel densities in SAS-R tumor tissues decreased remarkably after the Everolimus and radiation treatment. Everolimus-induced apoptosis of vascular ECs in response to radiation was also followed by thrombus formation that leads to tumor necrosis. We conclude that FR combined with Everolimus may be an effective modality to overcome radioresistant tumors via targeting tumor ECs. PMID:24464839

In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation and Chemotherapy.

PubMed

Tang, Hailin; Guo, Yuan; Peng, Li; Fang, Hui; Wang, Zhigang; Zheng, Yuanyi; Ran, Haitao; Chen, Yu

2018-05-09

As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe 3 O 4 -FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was conjugated onto the surface of the nanoplatform for achieving active targeting to hepatoma cells by receptor-ligand interaction, which facilitates accumulation of the nanoplatforms into the tumor site. The integrated superparamagnetic iron oxide nanoparticles could generate the contrast enhancement in T 2 -weighted magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU, liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was induced to generate PFH microbubbles, which achieved the contrast-enhanced ultrasound imaging and significantly improved the HIFU ablation efficacy. The loaded anticancer drugs could be released from the nanocomposites in a controllable manner (both pH and HIFU responsiveness). These multifunctional nanocomposites have been demonstrated to efficiently suppress the tumor growth based on the enhanced and synergistic chemotherapy and HIFU ablation, providing an efficient theranostic nanoplatform for cancer treatment.

Cross-modal prediction changes the timing of conscious access during the motion-induced blindness.

PubMed

Chang, Acer Y C; Kanai, Ryota; Seth, Anil K

2015-01-01

Despite accumulating evidence that perceptual predictions influence perceptual content, the relations between these predictions and conscious contents remain unclear, especially for cross-modal predictions. We examined whether predictions of visual events by auditory cues can facilitate conscious access to the visual stimuli. We trained participants to learn associations between auditory cues and colour changes. We then asked whether congruency between auditory cues and target colours would speed access to consciousness. We did this by rendering a visual target subjectively invisible using motion-induced blindness and then gradually changing its colour while presenting congruent or incongruent auditory cues. Results showed that the visual target gained access to consciousness faster in congruent than in incongruent trials; control experiments excluded potentially confounding effects of attention and motor response. The expectation effect was gradually established over blocks suggesting a role for extensive training. Overall, our findings show that predictions learned through cross-modal training can facilitate conscious access to visual stimuli. Copyright © 2014 Elsevier Inc. All rights reserved.

SU-C-BRE-01: 3D Conformal Micro Irradiation Results of Four Treatment Sites for Preclinical Small Animal and Clinical Treatment Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, S; Yaddanapudi, S; Rangaraj, D

Purpose: Small animal irradiation can provide preclinical insights necessary for clinical advancement. In order to provide clinically relevant data, these small animal irradiations must be designed such that the treatment methods and results are comparable to clinical protocols, regardless of variations in treatment size and modality. Methods: Small animal treatments for four treatment sites (brain, liver, lung and spine) were investigated, accounting for change in treatment energy and target size. Up to five orthovoltage (300kVp) beams were used in the preclinical treatments, using circular, square, and conformal tungsten apertures, based on the treatment site. Treatments were delivered using the imagemore » guided micro irradiator (microIGRT). The plans were delivered to a mouse sized phantom and dose measurements in axial and coronal planes were performed using radiochromic film. The results of the clinical and preclinical protocols were characterized in terms of conformality number, CTV coverage, dose nonuniformity ratio, and organ at risk sparing. Results: Preclinical small animal treatment conformality was within 1–16% of clinical results for all treatment sites. The volume of the CTV receiving 100% of the prescription dose was typically within 10% of clinical values. The dose non-uniformity was consistently higher for preclinical treatments compared to clinical treatments, indicating hot spots in the target. The ratios of the mean dose in the target to the mean dose in an organ at risk were comparable if not better for preclinical versus clinical treatments. Finally, QUANTEC dose constraints were applied and the recommended morbidity limits were satisfied in each small animal treatment site. Conclusion: We have shown that for four treatment sites, preclinical 3D conformal small animal treatments can be clinically comparable if clinical protocols are followed. Using clinical protocols as the standard, preclinical irradiation methods can be altered and iteratively improved to achieve a clinically relevant irradiation model.« less

An Event-Related Potential Study of Cross-modal Morphological and Phonological Priming

PubMed Central

Justus, Timothy; Yang, Jennifer; Larsen, Jary; de Mornay Davies, Paul; Swick, Diane

2009-01-01

The current work investigated whether differences in phonological overlap between the past- and present-tense forms of regular and irregular verbs can account for the graded neurophysiological effects of verb regularity observed in past-tense priming designs. Event-related potentials were recorded from sixteen healthy participants who performed a lexical-decision task in which past-tense primes immediately preceded present-tense targets. To minimize intra-modal phonological priming effects, cross-modal presentation between auditory primes and visual targets was employed, and results were compared to a companion intra-modal auditory study (Justus, Larsen, de Mornay Davies, & Swick, 2008). For both regular and irregular verbs, faster response times and reduced N400 components were observed for present-tense forms when primed by the corresponding past-tense forms. Although behavioral facilitation was observed with a pseudopast phonological control condition, neither this condition nor an orthographic-phonological control produced significant N400 priming effects. Instead, these two types of priming were associated with a post-lexical anterior negativity (PLAN). Results are discussed with regard to dual- and single-system theories of inflectional morphology, as well as intra- and cross-modal prelexical priming. PMID:20160930

Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

PubMed Central

Yi, Xiaomin; Wang, Fuli; Qin, Weijun; Yang, Xiaojian; Yuan, Jianlin

2014-01-01

Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized. PMID:24648733

Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field.

PubMed

Yi, Xiaomin; Wang, Fuli; Qin, Weijun; Yang, Xiaojian; Yuan, Jianlin

2014-01-01

Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized.

The pluripotential effects of hypolipidemic treatment for polycystic ovary syndrome (PCOS): dyslipidemia, cardiovascular risk factors and beyond.

PubMed

Economou, Frangiskos; Xyrafis, Xenofon; Christakou, Charikleia; Diamanti-Kandarakis, Evanthia

2011-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterized by oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenemia and polycystic ovaries. Clinical expression is determined by both genetic and environmental factors. Dyslipidemia is very common in lean as well as in obese women with PCOS and should be considered in the therapeutic management of the syndrome. Additionally to dyslipidemia, other risk factors for cardiovascular disease strongly associated with PCOS include insulin resistance, impaired glucose tolerance and metabolic syndrome. Therefore, the ideal therapeutic approach for PCOS would be multi targeted treatment ameliorating not only ovarian dysfunction but also cardiometabolic aspects, including dyslipidemia. Recently, a new era of hypolipidemic agents like statins has been initiated with regard to PCOS. The spectrum of statins' targets has been expanded and in vitro and in vivo studies have explored the specific effect of statins on androgen production, insulin resistance and inflammatory markers in PCOS. Statins are potentially promising therapeutic agents targeting hormonal and metabolic disturbances in PCOS, though conclusive results are still pending. Since several hormonal and metabolic aberrations characterizing this multifaceted syndrome cluster and interact with each other, their effects on the lipid profile are interweaving and the therapeutic modalities targeting dyslipidemia appear to have a more broad beneficial effect.

AXL is a logical molecular target in head and neck squamous cell carcinoma

PubMed Central

Brand, Toni M.; Iida, Mari; Stein, Andrew P.; Corrigan, Kelsey L.; Braverman, Cara M.; Coan, John; Pearson, Hannah E.; Bahrar, Harsh; Fowler, Tyler L.; Bednarz, Bryan P.; Saha, Sandeep; Yang, David; Gill, Parkash S.; Lingen, Mark W.; Saloura, Vassiliki; Villaflor, Victoria M.; Salgia, Ravi; Kimple, Randall J.; Wheeler, Deric L.

2016-01-01

Purpose Head and neck squamous cell carcinoma (HNSCC) represents the eighth most common malignancy worldwide. Standard of care treatments for HNSCC patients include surgery, radiation and chemotherapy. Additionally, the anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab is often used in combination with these treatment modalities. Despite clinical success with these therapeutics, HNSCC remains a difficult to treat malignancy. Thus, identification of new molecular targets is critical. Experimental Design In the current study, the receptor tyrosine kinase AXL was investigated as a molecular target in HNSCC using established cell lines, HNSCC patient derived xenografts (PDXs), and human tumors. HNSCC dependency on AXL was evaluated with both anti-AXL siRNAs and the small molecule AXL inhibitor R428. Furthermore, AXL inhibition was evaluated with standard of care treatment regimes used in HNSCC. Results AXL was found to be highly overexpressed in several models of HNSCC, where AXL was significantly associated with higher pathologic grade, presence of distant metastases and shorter relapse free survival in patients with HNSCC. Further investigations indicated that HNSCC cells were reliant on AXL for cellular proliferation, migration, and invasion. Additionally, targeting AXL increased HNSCC cell line sensitivity to chemotherapy, cetuximab, and radiation. Moreover, radiation resistant HNSCC cell line xenografts and PDXs expressed elevated levels of both total and activated AXL, indicating a role for AXL in radiation resistance. Conclusion Collectively, this study provides evidence for the role of AXL in HNSCC pathogenesis and supports further pre-clinical and clinical evaluation of anti-AXL therapeutics for the treatment of patients with HNSCC. PMID:25767293

Choice of treatment modalities was not influenced by pain, severity or co-morbidity in patients with knee osteoarthritis.

PubMed

Jamtvedt, Gro; Dahm, Kristin Thuve; Holm, Inger; Odegaard-Jensen, Jan; Flottorp, Signe

2010-03-01

Patients with knee osteoarthritis (OA) are commonly treated by physiotherapists in primary care. The physiotherapists use different treatment modalities. In a previous study, we identified variation in the use of transcutaneous electrical nerve stimulation (TENS), low level laser or acupuncture, massage and weight reduction advice for patients with knee OA. The purpose of this study was to examine factors that might explain variation in treatment modalities for patients with knee OA. Practising physiotherapists prospectively collected data for one patient with knee osteoarthritis each through 12 treatment sessions.We chose to examine factors that might explain variation in the choice of treatment modalities supported by high or moderate quality evidence, and modalities which were frequently used but which were not supported by evidence from systematic reviews. Experienced clinicians proposed factors that they thought might explain the variation in the choice of these specific treatments. We used these factors in explanatory analyses. Using TENS, low level laser or acupuncture was significantly associated with having searched databases to help answer clinical questions in the last six months (odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.08-3.42). Not having Internet access at work and using more than four treatment modalities were significant determinants for giving massage (OR = 0.36, 95% CI = 0.19-0.68 and OR = 8.92, 95% CI = 4.37-18.21, respectively). Being a female therapist significantly increased the odds for providing weight reduction advice (OR = 3.60, 95% CI = 1.12-11.57). No patient characteristics, such as age, pain or co-morbidity, were significantly associated with variation in practice. Factors related to patient characteristics, such as pain severity and co-morbidity, did not seem to explain variation in treatment modalities for patients with knee OA. Variation was associated with the following factors: physiotherapists having Internet access at work, physiotherapists having searched databases for the last six months and the gender of the therapist. There is a need for more studies of determinants for physiotherapy practice. (c) 2009 John Wiley & Sons, Ltd.

In vitro investigation on the magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate for breast cancer treatment.

PubMed

Zhao, Lingyun; Huo, Meijun; Liu, Jiayi; Yao, Zhu; Li, Danye; Zhao, Zhiwei; Tang, Jintian

2013-02-01

Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. In therapeutic oncology, hyperthermic adjuvant chemotherapy termed as thermochemotherapy plays an increasing role in multimodality cancer treatment. Currently, targeted nanothermotherapy is one of the effective hyperthermia approach based on magnetic nanoparticles (MNPs), which can be achieved by applying biocompatible nanoscaled metallic particles that convert electromagnetic energy into heat, for instance, magnetic fluid hyperthermia (MFH) mediated by superparamagnetic iron oxide nanoparticles (SPIONs). Upon exposure under alternative magnetic field (AMF), SPIONs can generate heat through oscillation of their magnetic moment. Nowadays, clinical trials at phase II are now under investigations for MFH on patients in Germany and Japan and demonstrate very inspiring for cancer therapy. In this work we explore the feasibility and effectiveness of magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate, an anti-cancer drug, for breast cancer comprehensive treatment. Amino silane coated MNPs as agent of MFH were prepared by the chemical precipitation method. Physiochemical characterizations on MNPs have been systematically carried out by various instrumental analyses. Inductive heating property of the MNPs was evaluated by monitoring the temperature increase of the MNPs suspension under AMF. The in-vitro cytotoxicity results on human breast cancer cell MCF-7 by CCK-8 assay indicated the bi-modal cancer treatment approach for combined MFH and chemotherapy is more effective than mono-modal treatment, indicating a thermal enhancement effect of hyperthermia on drug cytocoxicity. The magnetic thermochemotherapy mediated by MNPs combined with methotrexate can realize cancer comprehensive treatment thus has great potential in clinical application.

Audiovestibular consequences of congenital cytomegalovirus infection.

PubMed

Teissier, N; Bernard, S; Quesnel, S; Van Den Abbeele, T

2016-12-01

Congenital cytomegalovirus (CMV) infection is the second most frequent cause of mental retardation and sensorineural hearing loss, after genetic factors. Recently, pediatric forensic and fetopathological studies have led to progress in understanding the pathophysiological mechanisms underlying the various neurosensory sequelae. Thanks to the identification of certain prognostic factors of hearing loss, therapeutic protocols based on antiviral molecules are now proposed for target populations. This treatment has shown efficacy in limiting hearing threshold deterioration and even, in some cases, seems to provide partial recovery of hearing in symptomatic congenitally infected CMV neonates. However, optimal treatment duration and administration modalities are not clearly defined. This article reviews recent data concerning audiovestibular sequelae and their management in children congenitally infected by CMV. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes

PubMed Central

2015-01-01

We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection. PMID:25615011

Project for the development of the linac based NCT facility in University of Tsukuba.

PubMed

Kumada, H; Matsumura, A; Sakurai, H; Sakae, T; Yoshioka, M; Kobayashi, H; Matsumoto, H; Kiyanagi, Y; Shibata, T; Nakashima, H

2014-06-01

A project team headed by University of Tsukuba launched the development of a new accelerator based BNCT facility. In the project, we have adopted Radio-Frequency Quadrupole (RFQ)+Drift Tube Linac (DTL) type linac as proton accelerators. Proton energy generated from the linac was set to 8MeV and average current was 10mA. The linac tube has been constructed by Mitsubishi Heavy Industry Co. For neutron generator device, beryllium is selected as neutron target material; high intensity neutrons are generated by the reaction with beryllium and the 80kW proton beam. Our team chose beryllium as the neutron target material. At present beryllium target system is being designed with Monte-Carlo estimations and heat analysis with ANSYS. The neutron generator consists of moderator, collimator and shielding. It is being designed together with the beryllium target system. We also acquired a building in Tokai village; the building has been renovated for use as BNCT treatment facility. It is noteworthy that the linac tube had been installed in the facility in September 2012. In BNCT procedure, several medical devices are required for BNCT treatment such as treatment planning system, patient positioning device and radiation monitors. Thus these are being developed together with the linac based neutron source. For treatment planning system, we are now developing a new multi-modal Monte-Carlo treatment planning system based on JCDS. The system allows us to perform dose estimation for BNCT as well as particle radiotherapy and X-ray therapy. And the patient positioning device can navigate a patient to irradiation position quickly and properly. Furthermore the device is able to monitor movement of the patient׳s position during irradiation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Image-guided positioning and tracking.

PubMed

Ruan, Dan; Kupelian, Patrick; Low, Daniel A

2011-01-01

Radiation therapy aims at maximizing tumor control while minimizing normal tissue complication. The introduction of stereotactic treatment explores the volume effect and achieves dose escalation to tumor target with small margins. The use of ablative irradiation dose and sharp dose gradients requires accurate tumor definition and alignment between patient and treatment geometry. Patient geometry variation during treatment may significantly compromise the conformality of delivered dose and must be managed properly. Setup error and interfraction/intrafraction motion are incorporated in the target definition process by expanding the clinical target volume to planning target volume, whereas the alignment between patient and treatment geometry is obtained with an adaptive control process, by taking immediate actions in response to closely monitored patient geometry. This article focuses on the monitoring and adaptive response aspect of the problem. The term "image" in "image guidance" will be used in a most general sense, to be inclusive of some important point-based monitoring systems that can be considered as degenerate cases of imaging. Image-guided motion adaptive control, as a comprehensive system, involves a hierarchy of decisions, each of which balances simplicity versus flexibility and accuracy versus robustness. Patient specifics and machine specifics at the treatment facility also need to be incorporated into the decision-making process. Identifying operation bottlenecks from a system perspective and making informed compromises are crucial in the proper selection of image-guidance modality, the motion management mechanism, and the respective operation modes. Not intended as an exhaustive exposition, this article focuses on discussing the major issues and development principles for image-guided motion management systems. We hope these information and methodologies will facilitate conscientious practitioners to adopt image-guided motion management systems accounting for patient and institute specifics and to embrace advances in knowledge and new technologies subsequent to the publication of this article.

Insights into Atherosclerosis Using Nanotechnology

PubMed Central

Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

2010-01-01

A developing forefront in vascular disease research is the application of nanotechnology, the engineering of devices at the molecular scale, for diagnostic and therapeutic applications in atherosclerosis. Promising research in this field over the past decade has resulted in the preclinical validation of nanoscale devices that target cellular and molecular components of the atherosclerotic plaque, including one of its prominent cell types, the macrophage. Nanoscale contrast agents targeting constituents of plaque biology have been adapted for application in multiple imaging modalities, leading toward more detailed diagnostic readouts, whereas nanoscale drug delivery devices can be tailored for site-specific therapeutic activity. This review highlights recent progress in utilizing nanotechnology for the clinical management of atherosclerosis, drawing upon recent preclinical studies relevant to diagnosis and treatment of the plaque and promising future applications. PMID:20425261

PSMA-PET based radiotherapy: a review of initial experiences, survey on current practice and future perspectives.

PubMed

Zschaeck, Sebastian; Lohaus, Fabian; Beck, Marcus; Habl, Gregor; Kroeze, Stephanie; Zamboglou, Constantinos; Koerber, Stefan Alexander; Debus, Jürgen; Hölscher, Tobias; Wust, Peter; Ganswindt, Ute; Baur, Alexander D J; Zöphel, Klaus; Cihoric, Nikola; Guckenberger, Matthias; Combs, Stephanie E; Grosu, Anca Ligia; Ghadjar, Pirus; Belka, Claus

2018-05-11

68 Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative intended therapy. Owed to the novelty of the PSMA-targeting tracers, clinical evidence on the value of PSMA-PET is moderate but rapidly increasing. State of the art imaging is pivotal for radiotherapy treatment planning as it may affect dose prescription, target delineation and use of concomitant therapy.This review summarizes the evidence on PSMA-PET imaging from a radiation oncologist's point of view. Additionally a short survey containing twelve examples of patients and 6 additional questions was performed in seven mayor academic centers with experience in PSMA ligand imaging and the findings are reported here.

Irritable bowel syndrome in children: Current knowledge, challenges and opportunities

PubMed Central

Devanarayana, Niranga Manjuri; Rajindrajith, Shaman

2018-01-01

Irritable bowel syndrome (IBS) is a common and troublesome disorder in children with an increasing prevalence noted during the past two decades. It has a significant effect on the lives of affected children and their families and poses a significant burden on healthcare systems. Standard symptom-based criteria for diagnosis of pediatric IBS have changed several times during the past two decades and there are some differences in interpreting symptoms between different cultures. This has posed a problem when using them to diagnose IBS in clinical practice. A number of potential patho-physiological mechanisms have been described, but so far the exact underlying etiology of IBS is unclear. A few potential therapeutic modalities have been tested in children and only a small number of them have shown some benefit. In addition, most of the described patho-physiological mechanisms and treatment options are based on adult studies. These have surfaced as challenges when dealing with pediatric IBS and they need to be overcome for effective management of children with IBS. Recently suggested top-down and bottom-up models help integrating reported patho-physiological mechanisms and will provide an opportunity for better understanding of the diseases process. Treatment trials targeting single treatment modalities are unlikely to have clinically meaningful therapeutic effects on IBS with multiple integrating patho-physiologies. Trials focusing on multiple combined pharmacological and non-pharmacological therapies are likely to yield more benefit. In addition to treatment, in the future, attention should be paid for possible prevention strategies for IBS. PMID:29881232

Using Genome Sequence to Enable the Design of Medicines and Chemical Probes.

PubMed

Angelbello, Alicia J; Chen, Jonathan L; Childs-Disney, Jessica L; Zhang, Peiyuan; Wang, Zi-Fu; Disney, Matthew D

2018-02-28

Rapid progress in genome sequencing technology has put us firmly into a postgenomic era. A key challenge in biomedical research is harnessing genome sequence to fulfill the promise of personalized medicine. This Review describes how genome sequencing has enabled the identification of disease-causing biomolecules and how these data have been converted into chemical probes of function, preclinical lead modalities, and ultimately U.S. Food and Drug Administration (FDA)-approved drugs. In particular, we focus on the use of oligonucleotide-based modalities to target disease-causing RNAs; small molecules that target DNA, RNA, or protein; the rational repurposing of known therapeutic modalities; and the advantages of pharmacogenetics. Lastly, we discuss the remaining challenges and opportunities in the direct utilization of genome sequence to enable design of medicines.

Attention to olfaction. A psychophysical investigation.

PubMed

Spence, C; McGlone, F P; Kettenmann, B; Kobal, G

2001-06-01

Olfaction is unique among the senses in that signals from the peripheral sensory receptors bypass the thalamus on their way to the cortex. The fact that olfactory stimuli are not gated by the thalamus has led some researchers to suggest that people may be unable to selectively direct their attention toward the olfactory modality. We examined this issue in an experiment where participants made speeded intensity (strong vs weak)-discrimination responses to an unpredictable sequence of olfactory and visual stimuli. Attention was directed to either olfaction or to vision by means of an informative cue that predicted the likely modality for the upcoming target on the majority of trials. Participants responded more rapidly when the target was presented in the expected rather than the unexpected modality, showing that people can selectively attend to olfaction.

Balloon-Occluded Retrograde Transvenous Obliteration of a Gastric Vascular Malformation: An Innovative Approach to Treatment of a Rare Condition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansing, Catherine E., E-mail: catherine.e.hansing.mil@mail.mil; Marquardt, Joseph P.; Sutton, Daniel M.

Arteriovenous malformations (AVMs) are a high-flow form of a vascular malformation, which can be found anywhere in the body. While historically treated surgically, a multidisciplinary approach utilizing multiple specialties and treatment modalities is now commonly employed. In order to effectively treat an AVM, the nidus must be targeted and eradicated, which can be done via multiple approaches. We present the case of a 43-year-old male with a gastric wall AVM, which was initially incompletely treated using a percutaneous transarterial approach. The gastric AVM was noted to have dominant drainage through a gastrorenal shunt; therefore, Balloon-occluded Retrograde Transvenous Obliteration (BRTO) wasmore » utilized to eradicate the AVM nidus. This case illustrates the utility of Interventional Radiology, specifically BRTO, as another treatment option for challenging AVMs.« less

Botanicals for the prevention and treatment of cutaneous melanoma

PubMed Central

Syed, Deeba N.; Mukhtar, Hasan

2011-01-01

Summary Cutaneous melanoma, a cancer of melanocytes, when detected at later stages is arguably one of the most lethal cancers and the cause of more years of lost life than any other cancer among young adults. There is no standard therapy for advanced-stage melanoma and the median survival time for patients with metastatic melanoma is <1 yr. An urgent need for novel strategies against melanoma has directed research towards the development of new chemotherapeutic and biologic agents that can target the tumor by several different mechanisms. Recently, several dietary agents are being investigated for their role in the prevention and treatment of various forms of cancer and may represent the future modality of the treatment. Here, we have reviewed emerging data on botanicals that are showing promise for their potential inhibitory effect against cutaneous melanoma. PMID:21426532

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

PubMed

von Mehren, Margaret; Randall, R Lor; Benjamin, Robert S; Boles, Sarah; Bui, Marilyn M; Conrad, Ernest U; Ganjoo, Kristen N; George, Suzanne; Gonzalez, Ricardo J; Heslin, Martin J; Kane, John M; Koon, Henry; Mayerson, Joel; McCarter, Martin; McGarry, Sean V; Meyer, Christian; O'Donnell, Richard J; Pappo, Alberto S; Paz, I Benjamin; Petersen, Ivy A; Pfeifer, John D; Riedel, Richard F; Schuetze, Scott; Schupak, Karen D; Schwartz, Herbert S; Tap, William D; Wayne, Jeffrey D; Bergman, Mary Anne; Scavone, Jillian

2016-06-01

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy. Copyright © 2016 by the National Comprehensive Cancer Network.

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug discovery and play an important role in optimizing multi-target drug discovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Plantar hyperhidrosis: A review of current management.

PubMed

Singh, Sanjay; Kaur, Simranjit; Wilson, Paul

2016-11-01

To critically appraise current literature regarding the management of plantar hyperhidrosis in the form of a structured review. A literature search was conducted using various databases and search criteria. The literature reports the use of conservative, medical and surgical treatment modalities for the management of plantar hyperhidrosis. However, long-term follow-up data are rare and some treatment modalities currently available are not fully understood. There is a considerable dearth in the literature on the management of plantar hyperhidrosis. Further study in larger populations with longer follow-up times is critical to access the long-term effects of treatment. Nonetheless, iontophoresis, botulinum toxin injection and lumbar sympathectomy are promising treatment modalities for this disorder.

Orthodontic Treatment Timing and Modalities in Anterior Open Bite: Case Series Study

PubMed Central

Al Hamadi, Wisam; Saleh, Fayez; Kaddouha, Mohamad

2017-01-01

Objective: The purpose of this study was to present early and adult cases of anterior open bite that were treated efficiently using different treatment approaches and mechanics. Materials and Methods: Five patients of different age groups (from 7 to 27 years), suffering from a clear Anterior open bite deformity, were properly diagnosed and relevant treatment modality for each was selected. Results: Positive overbite was efficiently achieved for all patients. Conclusion: Patient compliance is a key factor in using removable habit breakers. However, fixed palatal crib gave the same results but in shorter time. Anterior open bite of skeletal components should be thoroughly evaluated before selecting camouflage or orthognathic surgery treatment modality. PMID:29299074

Impact of genetic targets on therapy in head and neck squamous cell carcinoma.

PubMed

Chaikhoutdinov, Irina; Goldenberg, David

2013-01-01

Despite advances in surgical technique, radiation therapy and chemotherapy, the mortality from head and neck squamous cell carcinoma (HNSCC) has not improved significantly. Squamous cell carcinoma is caused by tobacco use, alcohol consumption and infection with high-risk types of human papillomavirus. It is the 6th most common cancer in the world, with upwards of 45,000 new cases reported yearly in the United States alone.In recent years, there has been a significant increase in the understanding of the molecular and genetic pathogenesis of head and neck cancer, shedding light on the unexpected heterogeneity of the disease. Genetic analysis has led to new classification schemes for HNSCC, with different subgroups exhibiting different prognoses. In addition, multiple targets in aberrant signaling pathways have been identified using increasingly sophisticated bio-informatics tools. Advances in technology have allowed for novel delivery mechanisms to introduce genetic material into cells to produce a therapeutic effect by targeting cancer cells via a number of different approaches.A pressing need to develop novel therapies to augment current treatment modalities has led to a number of translational studies involving gene therapy in the treatment of HNSCC. This article will focus on a review of the most recent developments in molecular biology of head and neck squamous cell carcinoma in regards to possible targets for gene therapy, as well as the array of novel therapeutic strategies directed at these targets.

Motion-invariant SRT treatment detection from direct M-scan OCT imaging.

PubMed

Fountoukidou, Tatiana; Raisin, Philippe; Kaufmann, Daniel; Justiz, Jörn; Sznitman, Raphael; Wolf, Sebastian

2018-03-08

Selective retina therapy (SRT) is a laser treatment targeting specific posterior retinal layers. It is focused on inducing damage to the retinal pigment epithelium (RPE), while sparing other retinal tissue compared to traditional photocoagulation. However, the targeted RPE layer is invisible with most imaging modalities and induced SRT lesions cannot be monitored. In this work, imaging scans acquired from an experimental setup that couples the SRT laser beam with an optical coherence tomography (OCT) beam are analyzed in order to evaluate the treatment as they occur. We isolated a small part of the time-resolved scan corresponding to the end of the treatment, for which we have microscopic evidence of the SRT outcome. We then use a convolutional neural network to correspond each scan to the treatment result. We explore which aspects of the scan convey more valuable information for a robust therapy evaluation. By only using this adequately small part, we can achieve an online estimation, while being resilient to eye movement. The available dataset consists of time- resolved OCT scans of 98 ex vivo porcine eyes, treated with different energy levels. The proposed method yields high performance in the task of predicting whether the applied energy was adequate for SRT treatment, by focusing on the immediate OCT signal acquired during treatment time. We propose a strategy toward online noninvasive SRT treatment assessment, able to provide a satisfying evaluation of a treatment status, that therefore could be used for the planning of the treatment continuation.

Patients' perceptions of information and education for renal replacement therapy: an independent survey by the European Kidney Patients' Federation on information and support on renal replacement therapy.

PubMed

Van Biesen, Wim; van der Veer, Sabine N; Murphey, Mark; Loblova, Olga; Davies, Simon

2014-01-01

Selection of an appropriate renal replacement modality is of utmost importance for patients with end stage renal disease. Previous studies showed provision of information to and free modality choice by patients to be suboptimal. Therefore, the European Kidney Patients' Federation (CEAPIR) explored European patients' perceptions regarding information, education and involvement on the modality selection process. CEAPIR developed a survey, which was disseminated by the national kidney patient organisations in Europe. In total, 3867 patients from 36 countries completed the survey. Respondents were either on in-centre haemodialysis (53%) or had a functioning graft (38%) at the time of survey. The majority (78%) evaluated the general information about kidney disease and treatment as helpful, but 39% did not recall being told about alternative treatment options than their current one. Respondents were more often satisfied with information provided on in-centre haemodialysis (90%) and transplantation (87%) than with information provided on peritoneal dialysis (79%) or home haemodialysis (61%), and were more satisfied with information from health care professionals vs other sources such as social media. Most (75%) felt they had been involved in treatment selection, 29% perceived they had no free choice. Involvement in modality selection was associated with enhanced satisfaction with treatment (OR 3.13; 95% CI 2.72-3.60). Many respondents (64%) could not remember receiving education on how to manage their kidney disease in daily life. Perceptions on information seem to differ between countries. Kidney patients reported to be overall satisfied with the information they received on their disease and treatment, although information seemed mostly to have been focused on one modality. Patients involved in modality selection were more satisfied with their treatment. However, in the perception of the patients, the freedom to choose an alternative modality showed room for improvement.

Thermal-based treatment options for localized prostate cancer.

PubMed

Koch, Michael O; Gardner, Thomas A

2005-09-01

It seems clear that thermal-based therapies of prostate cancer have the potential to completely eradicate the prostate gland. Technical modifications continue to improve our ability to use these modalities more effectively, which can be seen in the ever decreasing morbidity from damage to adjacent structures. These treatments offer potential major advantages over surgery and radiation-based treatment modalities.

Molecular Imaging of Pancreatic Cancer with Antibodies

PubMed Central

2015-01-01

Development of novel imaging probes for cancer diagnostics remains critical for early detection of disease, yet most imaging agents are hindered by suboptimal tumor accumulation. To overcome these limitations, researchers have adapted antibodies for imaging purposes. As cancerous malignancies express atypical patterns of cell surface proteins in comparison to noncancerous tissues, novel antibody-based imaging agents can be constructed to target individual cancer cells or surrounding vasculature. Using molecular imaging techniques, these agents may be utilized for detection of malignancies and monitoring of therapeutic response. Currently, there are several imaging modalities commonly employed for molecular imaging. These imaging modalities include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, optical imaging (fluorescence and bioluminescence), and photoacoustic (PA) imaging. While antibody-based imaging agents may be employed for a broad range of diseases, this review focuses on the molecular imaging of pancreatic cancer, as there are limited resources for imaging and treatment of pancreatic malignancies. Additionally, pancreatic cancer remains the most lethal cancer with an overall 5-year survival rate of approximately 7%, despite significant advances in the imaging and treatment of many other cancers. In this review, we discuss recent advances in molecular imaging of pancreatic cancer using antibody-based imaging agents. This task is accomplished by summarizing the current progress in each type of molecular imaging modality described above. Also, several considerations for designing and synthesizing novel antibody-based imaging agents are discussed. Lastly, the future directions of antibody-based imaging agents are discussed, emphasizing the potential applications for personalized medicine. PMID:26620581

WE-A-304-01: Strategies and Technologies for Cranial Radiosurgery Planning: MLC-Based Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, G.

2015-06-15

The high fractional doses, stringent requirements for accuracy and precision, and surgical perspective characteristic of intracranial radiosurgery create considerations for treatment planning which are distinct from most other radiotherapy procedures. This session will introduce treatment planning techniques specific to two popular intracranial SRS modalities: Gamma Knife and MLC-based Linac. The basic treatment delivery characteristics of each device will be reviewed with a focus on how those characteristics determine the paradigm used for treatment planning. Basic techniques for treatment planning will be discussed, including considerations such as isodose selection, target and organ-at-risk definition, quality indices, and protection of critical structures. Futuremore » directions for SRS treatment planning will also be discussed. Learning Objectives: Introduce the basic physical principles of intracranial radiosurgery and how they are realized in the treatment planning paradigms for Gamma Knife and Linac radiosurgery. Demonstrate basic treatment planning techniques. Discuss metrics for evaluating SRS treatment plan quality. Discuss recent and future advances in SRS treatment planning. D. Schlesinger receives research support from Elekta, AB.« less

WE-A-304-02: Strategies and Technologies for Cranial Radiosurgery Planning: Gamma Knife

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlesinger, D.

2015-06-15

The high fractional doses, stringent requirements for accuracy and precision, and surgical perspective characteristic of intracranial radiosurgery create considerations for treatment planning which are distinct from most other radiotherapy procedures. This session will introduce treatment planning techniques specific to two popular intracranial SRS modalities: Gamma Knife and MLC-based Linac. The basic treatment delivery characteristics of each device will be reviewed with a focus on how those characteristics determine the paradigm used for treatment planning. Basic techniques for treatment planning will be discussed, including considerations such as isodose selection, target and organ-at-risk definition, quality indices, and protection of critical structures. Futuremore » directions for SRS treatment planning will also be discussed. Learning Objectives: Introduce the basic physical principles of intracranial radiosurgery and how they are realized in the treatment planning paradigms for Gamma Knife and Linac radiosurgery. Demonstrate basic treatment planning techniques. Discuss metrics for evaluating SRS treatment plan quality. Discuss recent and future advances in SRS treatment planning. D. Schlesinger receives research support from Elekta, AB.« less

Multiple Objects Fusion Tracker Using a Matching Network for Adaptively Represented Instance Pairs

PubMed Central

Oh, Sang-Il; Kang, Hang-Bong

2017-01-01

Multiple-object tracking is affected by various sources of distortion, such as occlusion, illumination variations and motion changes. Overcoming these distortions by tracking on RGB frames, such as shifting, has limitations because of material distortions caused by RGB frames. To overcome these distortions, we propose a multiple-object fusion tracker (MOFT), which uses a combination of 3D point clouds and corresponding RGB frames. The MOFT uses a matching function initialized on large-scale external sequences to determine which candidates in the current frame match with the target object in the previous frame. After conducting tracking on a few frames, the initialized matching function is fine-tuned according to the appearance models of target objects. The fine-tuning process of the matching function is constructed as a structured form with diverse matching function branches. In general multiple object tracking situations, scale variations for a scene occur depending on the distance between the target objects and the sensors. If the target objects in various scales are equally represented with the same strategy, information losses will occur for any representation of the target objects. In this paper, the output map of the convolutional layer obtained from a pre-trained convolutional neural network is used to adaptively represent instances without information loss. In addition, MOFT fuses the tracking results obtained from each modality at the decision level to compensate the tracking failures of each modality using basic belief assignment, rather than fusing modalities by selectively using the features of each modality. Experimental results indicate that the proposed tracker provides state-of-the-art performance considering multiple objects tracking (MOT) and KITTIbenchmarks. PMID:28420194

Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer.

PubMed

Jeon, Min Jeong; Gordon, Andrew C; Larson, Andrew C; Chung, Jin Wook; Kim, Young Il; Kim, Dong-Hyun

2016-05-01

A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death. Copyright © 2016 Elsevier Ltd. All rights reserved.

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

PubMed

Sharma, Priyanka

2018-04-14

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

First-in-human study of PET and optical dual-modality image-guided surgery in glioblastoma using 68Ga-IRDye800CW-BBN.

PubMed

Li, Deling; Zhang, Jingjing; Chi, Chongwei; Xiao, Xiong; Wang, Junmei; Lang, Lixin; Ali, Iqbal; Niu, Gang; Zhang, Liwei; Tian, Jie; Ji, Nan; Zhu, Zhaohui; Chen, Xiaoyuan

2018-01-01

Purpose : Despite the use of fluorescence-guided surgery (FGS), maximum safe resection of glioblastoma multiforme (GBM) remains a major challenge. It has restricted surgeons between preoperative diagnosis and intraoperative treatment. Currently, an integrated approach combining preoperative assessment with intraoperative guidance would be a significant step in this direction. Experimental design : We developed a novel 68 Ga-IRDye800CW-BBN PET/near-infrared fluorescence (NIRF) dual-modality imaging probe targeting gastrin-releasing peptide receptor (GRPR) in GBM. The preclinical in vivo tumor imaging and FGS were first evaluated using an orthotopic U87MG glioma xenograft model. Subsequently, the first-in-human prospective cohort study (NCT 02910804) of GBM patients were conducted with preoperative PET assessment and intraoperative FGS. Results : The orthotopic tumors in mice could be precisely resected using the near-infrared intraoperative system. Translational cohort research in 14 GBM patients demonstrated an excellent correlation between preoperative positive PET uptake and intraoperative NIRF signal. The tumor fluorescence signals were significantly higher than those from adjacent brain tissue in vivo and ex vivo (p < 0.0001). Compared with pathology, the sensitivity and specificity of fluorescence using 42 loci of fluorescence-guided sampling were 93.9% (95% CI 79.8%-99.3%) and 100% (95% CI 66.4%-100%), respectively. The tracer was safe and the extent of resection was satisfactory without newly developed neurologic deficits. Progression-free survival (PFS) at 6 months was 80% and two newly diagnosed patients achieved long PFS. Conclusions: This initial study has demonstrated that the novel dual-modality imaging technique is feasible for integrated pre- and intraoperative targeted imaging via the same molecular receptor and improved intraoperative GBM visualization and maximum safe resection.

[Non-pharmacological, non-technical treatments for musculoskeletal disease: methodological challenges of clinical trials using the example of knee osteoarthritis and falls in the elderly].

PubMed

Thiem, Ulrich; Trampisch, Ulrike; Trampisch, Hans-Joachim

2013-01-01

Physical therapy modalities are regarded as an integral part of the treatment of musculoskeletal diseases like osteoarthritis of the knee or falls in the elderly. Guidelines and treatment recommendations promote such interventions. However, the evidence supporting physical therapy modalities is often weaker than that found for drug treatments. One reason is that a simple blinding of treatment assignments by means of a placebo is usually not possible. Another issue is patient preferences that have an impact on the conduct of the study and the interpretation of the results. This article highlights methodological challenges of studies investigating physical therapy modalities, and points out some possible solutions. (As supplied by publisher). Copyright © 2013. Published by Elsevier GmbH.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Lin, M; Chen, L

Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategiesmore » were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.« less

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound

PubMed Central

2014-01-01

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibility of using transcranial MR-guided focused ultrasound to safely ablate substantial volumes of brain tumor tissue. PMID:25671132

Evaluation of common elbow pathologies: a focus on physical examination.

PubMed

Laratta, Joseph; Caldwell, Jon-Michael; Lombardi, Joseph; Levine, William; Ahmad, Christopher

2017-05-01

Elbow tendinopathy accounts for the majority of elbow pathology in patients presenting to upper extremity and sports medicine surgeons. With increased participation in overhead sports in an aging population, the incidence of elbow injuries has risen. A comprehensive knowledge of elbow anatomy and biomechanical function of the elbow complex is prerequisite in the assessment of patients with elbow injuries; however, a thorough understanding of alternative and confounding pathologies is essential for accurate diagnosis. Because tendinopathy, tendonitis, and tendon tears have an anatomic basis for their pathology, a targeted history and meticulous physical examination often yields an accurate clinical diagnosis. The importance of physical examination and provocative examination maneuvers must be stressed in a technologically advanced era where clinical diagnosis is too commonly attained solely by advanced imaging modalities. A revived dedication to the physical examination may enhance our ability to correctly diagnose various pathologies about the elbow. Early and accurate clinical diagnosis is the first step in the proper initiation of treatment modalities and improvement in overall patient outcome.

Combination of Fluorescence-Guided Surgery With Photodynamic Therapy for the Treatment of Cancer

PubMed Central

He, Jun; Yang, Leping; Yi, Wenjun; Fan, Wentao; Wen, Yu; Miao, Xiongying; Xiong, Li

2017-01-01

Specific visualization of body parts is needed during surgery. Fluorescence-guided surgery (FGS) uses a fluorescence contrast agent for in vivo tumor imaging to detect and identify both malignant and normal tissues. There are several advantages and clinical benefits of FGS over other conventional medical imaging modalities, such as its safety, effectiveness, and suitability for real-time imaging in the operating room. Recent advancements in contrast agents and intraoperative fluorescence imaging devices have led to a greater potential for intraoperative fluorescence imaging in clinical applications. Photodynamic therapy (PDT) is an alternative modality to treat tumors, which uses a light-sensitive drug (photosensitizers) and special light to destroy the targeted tissues. In this review, we discuss the fluorescent contrast agents, some newly developed imaging devices, and the successful clinical application of FGS. Additionally, we present the combined strategy of FGS with PDT to further improve the therapeutic effect for patients with cancer. Taken together, this review provides a unique perspective and summarization of FGS. PMID:28849712

Aging and response interference across sensory modalities.

PubMed

Guerreiro, Maria J S; Adam, Jos J; Van Gerven, Pascal W M

2014-06-01

Advancing age is associated with decrements in selective attention. It was recently hypothesized that age-related differences in selective attention depend on sensory modality. The goal of the present study was to investigate the role of sensory modality in age-related vulnerability to distraction, using a response interference task. To this end, 16 younger (mean age = 23.1 years) and 24 older (mean age = 65.3 years) adults performed four response interference tasks, involving all combinations of visual and auditory targets and distractors. The results showed that response interference effects differ across sensory modalities, but not across age groups. These results indicate that sensory modality plays an important role in vulnerability to distraction, but not in age-related distractibility by irrelevant spatial information.

Therapeutic effect of photodynamic therapy combined with targeted delivery of silencing vascular endothelial growth factor (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hsu, Yih-Chih

2016-03-01

Photodynamic therapy is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates tumours oxygen-independent hypoxic conditions. Vascular endothelial growth factor (VEGF) is one of the primary factors that affect tumor angiogenesis. Another emerging treatment to cure cancer is the use of interference RNA to silence a specific mRNA sequence. Such treatment requires a delivery system such as liposomes. The nanoparticle size measured was about 30 nm. Cellular uptake study was performed to verify that the nanoparticles have a sigma receptor mediated pathway. Non-targeted LCP NPs did not show significant difference with or without haloperidol but has a lower intensity as than targeted LCP NPs. These results confirm that LCP NPs have a receptor mediated pathway. Cell viability was found to decrease at 25 nM of transfected VEGF siRNA. Combined therapy of PDT and VEGF siRNA showed significant response as compared with PDT and gene therapy alone. In vivo toxicity assay with mice treated with targeted LCP NPs containing control siRNA or VEGF siRNA and non-targeted LCP NPs containing VEGF siRNA did not show any significant difference with the PBS injected group which suggests that there is no toxicity with the dose. It suggests that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.

Treatment planning for prostate focal laser ablation in the face of needle placement uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cepek, Jeremy, E-mail: jcepek@robarts.ca; Fenster, Aaron; Lindner, Uri

2014-01-15

Purpose: To study the effect of needle placement uncertainty on the expected probability of achieving complete focal target destruction in focal laser ablation (FLA) of prostate cancer. Methods: Using a simplified model of prostate cancer focal target, and focal laser ablation region shapes, Monte Carlo simulations of needle placement error were performed to estimate the probability of completely ablating a region of target tissue. Results: Graphs of the probability of complete focal target ablation are presented over clinically relevant ranges of focal target sizes and shapes, ablation region sizes, and levels of needle placement uncertainty. In addition, a table ismore » provided for estimating the maximum target size that is treatable. The results predict that targets whose length is at least 5 mm smaller than the diameter of each ablation region can be confidently ablated using, at most, four laser fibers if the standard deviation in each component of needle placement error is less than 3 mm. However, targets larger than this (i.e., near to or exceeding the diameter of each ablation region) require more careful planning. This process is facilitated by using the table provided. Conclusions: The probability of completely ablating a focal target using FLA is sensitive to the level of needle placement uncertainty, especially as the target length approaches and becomes greater than the diameter of ablated tissue that each individual laser fiber can achieve. The results of this work can be used to help determine individual patient eligibility for prostate FLA, to guide the planning of prostate FLA, and to quantify the clinical benefit of using advanced systems for accurate needle delivery for this treatment modality.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buis, Dennis R.; Lagerwaard, Frank J.; Dirven, Clemens M.F.

Purpose: To assess the dosimetric consequences of brain arteriovenous malformation (bAVM) delineation on magnetic resonance angiography (MRA) for the purpose of stereotactic radiosurgery. Methods and Materials: Three observers contoured a bAVM in 20 patients, using digital subtraction angiography (V{sub DSA}) and three-dimensional time-of-flight MRA (V{sub MRA}). Displacement between contours was calculated. Agreement and differences between observers and imaging modalities were assessed. A standardized treatment plan with dynamic conformal arcs was generated and dosimetric coverage of all contours and the volume of normal brain tissue within the high dose region was determined. Results: The generalized reliability coefficient was 'fair' for targetmore » volume (0.79), but 'poor' for displacement (0.35). V{sub MRA} was larger than V{sub DSA} (5.0 vs. 4.0 mL, p = 0.001). No difference in displacement was found (2.8 vs. 2.5 mm, p = 0.156). Dosimetric coverage of V{sub MRA} was 62.9% (95% CI, 56.9-68.8) when V{sub DSA} was used as planning target volume, and coverage of V{sub DSA} was 83.5% (95% CI, 78.1-88.8) when V{sub MRA} was used for planning (p < 0.001). The mean volume of normal brain within the 80% isodose was larger when the bAVM was delineated on MRA (0.7 vs. 1.0 mL (p = 0.02) for targets {<=}3 mL and 3.7 vs. 7.0 mL (p = 0.01) for targets >3 mL). Conclusions: Brain arteriovenous malformations delineated on MRA are larger and more randomly displaced. However, for bAVMs {<=}3 mL, the difference in volume of normal brain tissue within the high-dose region does not seem to be clinically relevant. Therefore, MRA-images might be used as the sole imaging modality for the radiosurgical treatment of bAVMs {<=}3 mL when the bAVM is located in a noneloquent position.« less

Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics.

PubMed

Shen, Xue; Li, Tingting; Chen, Zhongyuan; Geng, Yue; Xie, Xiaoxue; Li, Shun; Yang, Hong; Wu, Chunhui; Liu, Yiyao

2017-01-01

Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe 3 O 4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(d,l-lactic- co -glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T 2 -weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual-modality imaging in cancer treatment.

Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics

PubMed Central

Shen, Xue; Li, Tingting; Chen, Zhongyuan; Geng, Yue; Xie, Xiaoxue; Li, Shun; Yang, Hong; Wu, Chunhui; Liu, Yiyao

2017-01-01

Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe3O4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T2-weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual-modality imaging in cancer treatment. PMID:28652734

Treatment modalities and evaluation models for periodontitis

PubMed Central

Tariq, Mohammad; Iqbal, Zeenat; Ali, Javed; Baboota, Sanjula; Talegaonkar, Sushama; Ahmad, Zulfiqar; Sahni, Jasjeet K

2012-01-01

Periodontitis is the most common localized dental inflammatory disease related with several pathological conditions like inflammation of gums (gingivitis), degeneration of periodontal ligament, dental cementum and alveolar bone loss. In this perspective, the various preventive and treatment modalities, including oral hygiene, gingival irrigations, mechanical instrumentation, full mouth disinfection, host modulation and antimicrobial therapy, which are used either as adjunctive treatments or as stand-alone therapies in the non-surgical management of periodontal infections, have been discussed. Intra-pocket, sustained release systems have emerged as a novel paradigm for the future research. In this article, special consideration is given to different locally delivered anti-microbial and anti inflammatory medications which are either commercially available or are currently under consideration for Food and Drug Administration (FDA) approval. The various in vitro dissolution models and microbiological strain investigated to impersonate the infected and inflamed periodontal cavity and to predict the in vivo performance of treatment modalities have also been thrashed out. Animal models that have been employed to explore the pathology at the different stages of periodontitis and to evaluate its treatment modalities are enlightened in this proposed review. PMID:23373002

[Alternative treatments for interstitial cystitis].

PubMed

Gamé, X; Bart, S; Castel-Lacanal, E; De Sèze, M; Karsenty, G; Labat, J-J; Rigaud, J; Scheiber-Nogueira, M C; Ruffion, A

2009-06-01

Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.

Turbofan aft duct suppressor study

NASA Technical Reports Server (NTRS)

Syed, A. A.; Motsinger, R. E.; Fiske, G. H.; Joshi, M. C.; Kraft, R. E.

1983-01-01

Suppressions due to acoustic treatment in the annular exhaust duct of a model fan were theoretically predicted and compared with measured suppressions. The predictions are based on the modal analysis of sound propagation in a straight annular flow duct with segmented treatment. Modal distributions of the fan noise source (fan-stator interaction only) were measured using in-duct modal probes. The flow profiles were also measured in the vicinity of the modal probes. The acoustic impedance of the single degree of freedom treatment was measured in the presence of grazing flow. The measured values of mode distribution of the fan noise source, the flow velocity profile and the acoustic impedance of the treatment in the duct were used as input to the prediction program. The predicted suppressions, under the assumption of uniform flow in the duct, compared well with the suppressions measured in the duct for all test conditions. The interaction modes generated by the rotor-stator interaction spanned a cut-off ratio range from nearly 1 to 7.

Myeloid-derived suppressor cells: Cellular missiles to target tumors.

PubMed

Chandra, Dinesh; Gravekamp, Claudia

2013-11-01

While conventional anticancer therapies, including surgical resection, radiotherapy, and/or chemotherapy, are relatively efficient at eliminating primary tumors, these treatment modalities are largely ineffective against metastases. At least in part, this reflects the rather inefficient delivery of conventional anticancer agents to metastatic lesions. We have recently demonstrated that myeloid-derived suppressor cells (MDSCs) can be used as cellular missiles to selectively deliver a radioisotope-coupled attenuated variant of Listeria monocytogenes to both primary and metastatic neoplastic lesions in mice with pancreatic cancer. This novel immunotherapeutic intervention robustly inhibited tumor growth while promoting a dramatic decrease in the number of metastases.

Experience with free fibula transfer with screw fixation as a primary modality of treatment for congenital pseudarthosis of tibia in children - Series of 26 cases

PubMed Central

Kalra, Guru Dayal Singh; Agarwal, Amit

2012-01-01

Background: Congenital pseudarthrosis is one of the greatest challenges of paediatric orthopaedic practice. Treatment options and literature addressing this condition are numerous, reflecting the difficulty in management. We aimed to study the effectiveness of free fibula transfer as a primary modality of treatment in children with this condition in terms of achieving length, union, and normal axis of the involved leg. Materials and Methods: During the period of 2001 to 2010, 26 children with congenital pseudarthrosis of tibia between age group of 2-8 years were evaluated and were reconstructed using contra-lateral free fibula graft, and then patients were followed up for 5 years subsequently. Patients were examined and time of bony union, weight bearing ability and walking without support were noted. Any complication directly or indirectly related to surgery with any complication seen in the due course of follow up of 5 years was also taken care of. Results: In our experience with treatment of congenital pseudarthrosis over a span of 10 years with free fibula transfer, the results have been gratifying with no flap loss. All our patients had UNEVENTFUL post-op recovery. Only 2 patients out of 26 had non-union, for which cancellous bone grafting was done (7.6%). Most of the patients were ambulatory with support by 3-6 months and continued to walk without support after a span of 18-24 months. The incidence of stress fracture in our study over the follow-up period was 4 out of 26 pts (15.3%). None of them had any deformity in the donor leg. Conclusion: When compared to other surgical modalities of treatment of the problem in question, vascularised free fibula transfer has emerged as a real saviour with good patient compliance and less complication rate in our study. It achieves the desired target with no residual deformities and near normal to normal gait with no stigma of bone removal from other leg. PMID:23450675

Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults

PubMed Central

Ryu, Hokyoung; Kim, Jae-Kwan; Jeong, Eunju

2018-01-01

Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standard Deviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition. PMID:29641462

Awareness, knowledge, and attitude of patients toward dental implants - A questionnaire-based prospective study.

PubMed

Hosadurga, Rajesh; Shanti, Tenneti; Hegde, Shashikanth; Kashyap, Rajesh Shankar; Arunkumar, Suryanarayan Maiya

2017-01-01

In developing nations like India awareness and education about dental implants as a treatment modality is still scanty. The study was conducted to determine the awareness, knowledge, and attitude of patients toward dental implants as a treatment modality among the general population and to assess the influence of personality characteristics on accepting dental implants as a treatment modality in general and as well as treatment group. A structured questionnaire-based survey was conducted on 500 randomly selected participants attending the outpatient department. The study was conducted in 2 parts. In the first part of the study, level of awareness, knowledge, and attitude was assessed. In the second part of the study, interactive educational sessions using audiovisual aids were conducted following which a retest was conducted. The participants who agreed to undergo implant treatment were followed up to assess their change in attitude towards dental implants posttreatment. Thus pain, anxiety, functional, and esthetic benefits were measured using visual analog scale. They were further followed up for 1 year to reassess awareness, knowledge, and attitude towards dental implants. A total of 450 individuals completed the questionnaires. Only 106 individuals agreed to participate in the educational sessions and 83 individuals took the retest. Out of these, only 39 individuals chose implants as a treatment option. A significant improvement in the level of information, subjective and objective need for information, was noted after 1 year. In this study, a severe deficit in level of information, subjective and objective need for information towards, dental implants as a treatment modality was noted. In the treatment group, a significant improvement in perception of dental implant as a treatment modality suggests that professionally imparted knowledge can bring about a change in the attitude.

Technical Note: Construction of heterogeneous head phantom for quality control in stereotactic radiosurgery.

PubMed

Najafi, Mohsen; Teimouri, Javad; Shirazi, Alireza; Geraily, Ghazale; Esfahani, Mahbod; Shafaei, Mostafa

2017-10-01

Stereotactic radiosurgery is a high precision modality for conformally delivering high doses of radiation to the brain lesion with a large dose volume. Several studies for the quality control of this technique were performed to measure the dose delivered to the target with a homogenous head phantom and some dosimeters. Some studies were also performed with one or two instances of heterogeneity in the head phantom to measure the dose delivered to the target. But these studies assumed the head as a sphere and simple shape heterogeneity. The construction of an adult human head phantom with the same size, shape, and real inhomogeneity as an adult human head is needed. Only then is measuring the accurate dose delivered to the area of interest and comparison with the calculated dose possible. According to the ICRU Report 44, polytetrafluoroethylene (PTFE) and methyl methacrylate were selected as a bone and soft tissue, respectively. A set of computed tomography (CT) scans from a standard human head were taken, and simplification of the CT images was used to design the layers of the phantom. The parts of each slice were cut and attached together. Tests of density and CT number were done to compare the material of the phantom with tissues of the head. The dose delivered to the target was measured with an EBT3 film. The density of the PTFE and Plexiglas that were inserted in the phantom are in good agreement with bone and soft tissue. Also, the CT numbers of these materials have a low difference. The dose distribution from the EBT3 film and the treatment planning system is similar. The constructed phantom with a size and inhomogeneity like an adult human head is suitable to measure the dose delivered to the area of interest. It also helps make an accurate comparison with the calculated dose by the treatment planning system. By using this phantom, the actual dose delivered to the target was obtained. This anthropomorphic head phantom can be used in other modalities of radiosurgery as well. © 2017 American Association of Physicists in Medicine.

Clinical applications of advanced rotational radiation therapy

NASA Astrophysics Data System (ADS)

Nalichowski, Adrian

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The dose rate was not found to be an independent risk factor for IP. The model failed to establish accurate dose response function, but the discrete data indicated a radiation dose threshold of 7.6Gy (EQD2_repair) and 120 mg/kg of Cy below which no IP cases were reported. Conclusion: The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation. The new system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing when compared to Eclipse treatment planning system for VMAT delivery. The machine optimization parameters tested for TMI cases provide a comprehensive overview of the capabilities of the treatment planning station and associated helical delivery system. The new system also proved to be dosimetrically compatible with other leading modalities for treatments of small and complicated target volumes and was even superior when treatment delivery times were compared. These finding demonstrate that the advanced treatment planning and delivery system from TomoTherapy is well suitable for treatments of complicated cases such as TMI and SRS and it's often dosimetrically and/or logistically superior to other modalities. The new planning system can easily meet the constraint of threshold lung dose established in this study. The results presented here on the capabilities of Tomotherapy and on the identified lung dose threshold provide an opportunity to explore alternative fractionation schemes without sacrificing target coverage or lung toxicity. (Abstract shortened by ProQuest.).

Segmentation of British Sign Language (BSL): mind the gap!

PubMed

Orfanidou, Eleni; McQueen, James M; Adam, Robert; Morgan, Gary

2015-01-01

This study asks how users of British Sign Language (BSL) recognize individual signs in connected sign sequences. We examined whether this is achieved through modality-specific or modality-general segmentation procedures. A modality-specific feature of signed languages is that, during continuous signing, there are salient transitions between sign locations. We used the sign-spotting task to ask if and how BSL signers use these transitions in segmentation. A total of 96 real BSL signs were preceded by nonsense signs which were produced in either the target location or another location (with a small or large transition). Half of the transitions were within the same major body area (e.g., head) and half were across body areas (e.g., chest to hand). Deaf adult BSL users (a group of natives and early learners, and a group of late learners) spotted target signs best when there was a minimal transition and worst when there was a large transition. When location changes were present, both groups performed better when transitions were to a different body area than when they were within the same area. These findings suggest that transitions do not provide explicit sign-boundary cues in a modality-specific fashion. Instead, we argue that smaller transitions help recognition in a modality-general way by limiting lexical search to signs within location neighbourhoods, and that transitions across body areas also aid segmentation in a modality-general way, by providing a phonotactic cue to a sign boundary. We propose that sign segmentation is based on modality-general procedures which are core language-processing mechanisms.

A novel extracellular drug conjugate significantly inhibits head and neck squamous cell carcinoma

PubMed Central

Sweeny, Larissa; Hartman, Yolanda E.; Zinn, Kurt R.; Prudent, James R.; Marshall, David J.; Shekhani, Mohammed S.; Rosenthal, Eben L.

2014-01-01

Objectives Despite advances in treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat with poor survival and high morbidity, necessitating a therapy with greater efficacy. EDC22 is an extracellular drug conjugate of the monoclonal antibody targeting CD147 (glycoprotein highly expressed on HNSCC cells) linked with a small drug molecule inhibitor of Na, K-ATPase. In this study, EDC22’s potential as a treatment modality for HNSCC was performed. Materials and methods HNSCC cell lines (FADU, OSC-19, Cal27, SCC-1) were cultured in vitro and proliferation and cell viability were assessed following treatment with a range of concentrations of EDC22 (0.25–5.00 μg/mL). Mice bearing HNSCC xenografts (OSC-19, SCC-1) were treated with either EDC22 (3–10 mg/kg), anti-CD147 monoclonal antibody, cisplatin (1 mg/kg) or radiation therapy (2 Gy/week) monotherapy or in combination. Results In vitro, treatment with minimal concentration of EDC22 (0.25 μg/mL) significantly decreased cellular proliferation and cell viability (p < 0.0001). In vivo, systemic treatment with EDC22 significantly decreased primary tumor growth rate in both an orthotopic mouse model (OSC-19) and a flank tumor mouse model (SCC-1) (p < 0.05). In addition, EDC22 therapy resulted in a greater reduction in tumor growth in vivo compared to radiation monotherapy (p < 0.05) and a similar reduction in tumor growth compared to cisplatin monotherapy. Combination therapy provided no significant further reduction in tumor growth relative to EDC22 monotherapy. Conclusion EDC22 is a potent inhibitor of HNSCC cell proliferation in vitro and in vivo, warranting further investigations of its clinical potential in the treatment of HNSCC. PMID:23920309

Optimized Non-Obstructive Particle Damping (NOPD) Treatment for Composite Honeycomb Structures

NASA Technical Reports Server (NTRS)

Panossian, H.

2008-01-01

Non-Obstructive Particle Damping (NOPD) technology is a passive vibration damping approach whereby metallic or non-metallic particles in spherical or irregular shapes, of heavy or light consistency, and even liquid particles are placed inside cavities or attached to structures by an appropriate means at strategic locations, to absorb vibration energy. The objective of the work described herein is the development of a design optimization procedure and discussion of test results for such a NOPD treatment on honeycomb (HC) composite structures, based on finite element modeling (FEM) analyses, optimization and tests. Modeling and predictions were performed and tests were carried out to correlate the test data with the FEM. The optimization procedure consisted of defining a global objective function, using finite difference methods, to determine the optimal values of the design variables through quadratic linear programming. The optimization process was carried out by targeting the highest dynamic displacements of several vibration modes of the structure and finding an optimal treatment configuration that will minimize them. An optimal design was thus derived and laboratory tests were conducted to evaluate its performance under different vibration environments. Three honeycomb composite beams, with Nomex core and aluminum face sheets, empty (untreated), uniformly treated with NOPD, and optimally treated with NOPD, according to the analytically predicted optimal design configuration, were tested in the laboratory. It is shown that the beam with optimal treatment has the lowest response amplitude. Described below are results of modal vibration tests and FEM analyses from predictions of the modal characteristics of honeycomb beams under zero, 50% uniform treatment and an optimal NOPD treatment design configuration and verification with test data.

Multi-disciplinary optimization of aeroservoelastic systems

NASA Technical Reports Server (NTRS)

Karpel, Mordechay

1991-01-01

New methods were developed for efficient aeroservoelastic analysis and optimization. The main target was to develop a method for investigating large structural variations using a single set of modal coordinates. This task was accomplished by basing the structural modal coordinates on normal modes calculated with a set of fictitious masses loading the locations of anticipated structural changes. The following subject areas are covered: (1) modal coordinates for aeroelastic analysis with large local structural variations; and (2) time simulation of flutter with large stiffness changes.

Closed treatment of unilateral mandibular condyle fractures in adults: a systematic review.

PubMed

Rozeboom, A V J; Dubois, L; Bos, R R M; Spijker, R; de Lange, J

2017-04-01

Of all mandibular fractures, 25-35% are condylar. Many studies have focused on whether to treat such fractures via open or closed modalities. A uniform protocol for closed treatment is lacking, but such a protocol could ensure good clinical practice. The aims of this systematic review were to provide an overview of the published studies exclusively pertaining to closed treatment and to summarize the existing modalities for closed treatment and their clinical outcomes. Sixteen studies were selected for detailed analysis. The treatments given were highly variable, ranging from doing nothing to applying maxillomandibular fixation with stainless steel wires. The results of the different studies and the treatment modalities used were difficult to interpret; however no clear differences in the outcome measures were seen between the treatment modalities applied. Complications encountered after closed treatment included malocclusion, limited mouth opening, reduced range of motion, and persistent pain. Due to the heterogeneity between groups, high loss-to-follow-up, poor descriptions of the treatments given, and variability in outcome measurement methods, no clear associations between adverse outcomes and the treatments applied could be determined. This review suggests that due to the high level of methodological variability in the relevant studies published to date, there are currently no uniform standards for the closed treatment of condylar fractures that can be expected to yield good clinical results. The establishment of such standards could potentially improve treatment outcomes. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Minimally invasive surgery for intracerebral haemorrhage.

PubMed

Barnes, Benjamin; Hanley, Daniel F; Carhuapoma, Juan R

2014-04-01

Spontaneous intracerebral haemorrhage (ICH) imposes a significant health and economic burden on society. Despite this, ICH remains the only stroke subtype without a definitive treatment. Without a clearly identified and effective treatment for spontaneous ICH, clinical practice varies greatly from aggressive surgery to supportive care alone. This review will discuss the current modalities of treatments for ICH including preliminary experience and investigative efforts to advance the care of these patients. Open surgery (craniotomy), prothrombotic agents and other therapeutic interventions have failed to significantly improve the outcome of these stroke victims. Recently, the Surgical Trial in Intracerebral Haemorrhage (STICH) II assessed the surgical management of patients with superficial intraparenchymal haematomas with negative results. MISTIE II and other trials of minimally invasive surgery (MIS) have shown promise for improving patient outcomes and a phase III trial started in late 2013. ICH lacks a definitive primary treatment as well as a therapy targeting surrounding perihematomal oedema and associated secondary damage. An ongoing phase III trial using MIS techniques shows promise for providing treatment for these patients.

Breast Cancer Treatment in the Era of Molecular Imaging

PubMed Central

Edelhauser, Gundula; Funovics, Martin

2008-01-01

Summary Molecular imaging employs molecularly targeted probes to visualize and often quantify distinct disease-specific markers and pathways. Modalities like intravital confocal or multiphoton microscopy, near-infrared fluorescence combined with endoscopy, surface reflectance imaging, or fluorescence-mediated tomography, and radionuclide imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are increasingly used for small animal high-throughput screening, drug development and testing, and monitoring gene therapy experiments. In the clinical treatment of breast cancer, PET and SPECT as well as magnetic resonance-based molecular imaging are already established for the staging of distant disease and intrathoracic nodal status, for patient selection regarding receptor-directed treatments, and to gain early information about treatment efficacy. In the near future, reporter gene imaging during gene therapy and further spatial and qualitative characterization of the disease can become clinically possible with radionuclide and optical methods. Ultimately, it may be expected that every level of breast cancer treatment will be affected by molecular imaging, including screening. PMID:21048912

Mind styles and the hypnotic induction profile: measure and match to enhance medical treatment.

PubMed

Greenleaf, Marcia

2006-07-01

Modern medical technology and economic impositions tend to dehumanize the medical patient. This paper describes a targeted use of the hypnotic modality for relationship building, symptom management, and restoring a sense of self to the patient. To humanize medical care one patient at a time, examples are given for the use of the Hypnotic Induction Profile, the Eye Roll sign and AOD (Apollonian-Odyssean-Dionysian) Mind-Style Questionnaire as a basis for choosing bio-psycho-social treatment strategies. This trio of assessments can be used together, in approximately 10 to 15 minutes, or separately, if treatment decisions need to be made in a few minutes or less. The hypothesis presented is that matching treatment strategies, with or without formal hypnosis, to hypnotic capacity and mind style can increase respectful care and efficacy of treatment outcome. Clinical examples will illustrate this approach to enhance recovery, morale, and maximize patients' ability to become active partners on their own behalf.

Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report.

PubMed

Vlahovic, Aleksandar M; Vlahovic, Natasa S; Haxhija, Emir Q

2015-08-01

Management of patients with complex vascular anomalies (VAs) is often associated with significant morbidity and mortality because of the lack of effective treatment modalities that may lead to significant improvement of the disease and/or healing. Recently, reports of treatment of patients with complex VAs with sirolimus revealed encouraging results. Sirolimus inhibits the mammalian target of rapamycin, which acts as a master switch of numerous cellular processes. We report a successful use of sirolimus for the treatment of a patient with a complex CLVM of the trunk and the right lower extremity believed to be untreatable. Our patient had 44 hospitalizations during the 10-year period, with various unsuccessful treatments and continuous deterioration of his clinical condition, ending up in a wheelchair. His condition reversed to normal everyday activities 9 months after initiation of sirolimus therapy. We conclude that sirolimus is a very promising therapeutic option for children with complex VAs of capillary-lymphatico-venous type. Copyright © 2015 by the American Academy of Pediatrics.

Assessing Instructional Modalities: Individualized Treatment Effects for Personalized Learning

ERIC Educational Resources Information Center

Beemer, Joshua; Spoon, Kelly; Fan, Juanjuan; Stronach, Jeanne; Frazee, James P.; Bohonak, Andrew J.; Levine, Richard A.

2018-01-01

Estimating the efficacy of different instructional modalities, techniques, and interventions is challenging because teaching style covaries with instructor, and the typical student only takes a course once. We introduce the individualized treatment effect (ITE) from analyses of personalized medicine as a means to quantify individual student…

Non-invasive different modalities of treatment for temporomandibular disorders: review of literature

PubMed Central

2018-01-01

Temporomandibular disorders (TMDs) are diseases that affect the temporomandibular joint and supporting structures. The goal of treatment for TMDs is elimination or reduction of pain and return to normal temporomandibular joint function. Initial treatment for TMDs is non-invasive and conservative, not surgical. Oral and maxillofacial surgeons should fully understand and actively care about non-invasive treatments for TMDs. The purpose of this study is to review the validity and outcomes of non-invasive and surgical treatment modalities for TMDs. PMID:29732308

Dosimetric comparison of photon and proton treatment techniques for chondrosarcoma of thoracic spine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Poonam, E-mail: yadav@humonc.wisc.edu; Department of Medical Physics, University of Wisconsin, Madison, WI; University of Wisconsin Riverview Cancer Center, Wisconsin Rapids, WI

2013-10-01

Chondrosarcomas are relatively radiotherapy resistant, and also delivering high radiation doses is not feasible owing to anatomic constraints. In this study, the feasibility of helical tomotherapy for treatment of chondrosarcoma of thoracic spine is explored and compared with other available photon and proton radiotherapy techniques in the clinical setting. A patient was treated for high-grade chondrosarcoma of the thoracic spine using tomotherapy. Retrospectively, the tomotherapy plan was compared with intensity-modulated radiation therapy, dynamic arc photon therapy, and proton therapy. Two primary comparisons were made: (1) comparison of normal tissue sparing with comparable target volume coverage (plan-1), and (2) comparison ofmore » target volume coverage with a constrained maximum dose to the cord center (plan-2). With constrained target volume coverage, proton plans were found to yield lower mean doses for all organs at risk (spinal cord, esophagus, heart, and both lungs). Tomotherapy planning resulted in the lowest mean dose to all organs at risk amongst photon-based methods. For cord dose constrained plans, the static-field intensity-modulated radiation therapy and dynamic arc plans resulted target underdosing in 20% and 12% of planning target volume2 volumes, respectively, whereas both proton and tomotherapy plans provided clinically acceptable target volume coverage with no portion of planning target volume2 receiving less than 90% of the prescribed dose. Tomotherapy plans are comparable to proton plans and produce superior results compared with other photon modalities. This feasibility study suggests that tomotherapy is an attractive alternative to proton radiotherapy for delivering high doses to lesions in the thoracic spine.« less

A dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michalski, Andrea; Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales; Atyeo, John, E-mail: john.atyeo@sydney.edu.au

2014-07-01

Radiation therapy to the breast is a complex task, with many different techniques that can be employed to ensure adequate dose target coverage while minimizing doses to the organs at risk. This study compares the dose planning outcomes of 3 radiation treatment modalities, 3 dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and static tomotherapy, for left-sided whole-breast radiation treatment with a simultaneous integrated boost (SIB). Overall, 20 patients with left-sided breast cancer were separated into 2 cohorts, small and large, based on breast volume. Dose plans were produced for each patient using 3D-CRT, IMRT, and static tomotherapy. Allmore » patients were prescribed a dose of 45 Gy in 20 fractions to the breast with an SIB of 56 Gy in 20 fractions to the tumor bed and normalized so that D{sub 98%} > 95% of the prescription dose. Dosimetric comparisons were made between the 3 modalities and the interaction of patient size. All 3 modalities offered adequate planning target volume (PTV) coverage with D{sub 98%} > 95% and D{sub 2%} < 107%. Static tomotherapy offered significantly improved (p = 0.006) dose homogeneity to the PTV{sub boost} {sub eval} (0.079 ± 0.011) and breast minus the SIB volume (Breast{sub SIB}) (p < 0.001, 0.15 ± 0.03) compared with the PTV{sub boost} {sub eval} (0.085 ± 0.008, 0.088 ± 0.12) and Breast{sub SIB} (0.22 ± 0.05, 0.23 ± 0.03) for IMRT and 3D-CRT, respectively. Static tomotherapy also offered statistically significant reductions (p < 0.001) in doses to the ipsilateral lung mean dose of 6.79 ± 2.11 Gy compared with 7.75 ± 2.54 Gy and 8.29 ± 2.76 Gy for IMRT and 3D-CRT, respectively, and significantly (p < 0.001) reduced heart doses (mean = 2.83 ± 1.26 Gy) compared to both IMRT and 3D-CRT (mean = 3.70 ± 1.44 Gy and 3.91 ± 1.58 Gy). Static tomotherapy is the dosimetrically superior modality for the whole breast with an SIB compared with IMRT and 3D-CRT. IMRT is superior to 3D-CRT in both PTV dose conformity and reduction of mean doses to the ipsilateral lung.« less

Efficacy and safety of bispecific T-cell engager blinatumomab and the potential to improve leukemia-free survival in B-cell acute lymphoblastic leukemia.

PubMed

Ribera, Josep-Maria

2017-12-01

Immunotherapy is a promising modality of treatment of neoplastic diseases, including acute lymphoblastic leukemia (ALL). The CD19/CD3-bispecific T cell-engaging (BiTE®) monoclonal antibody blinatumomab can transiently bind cytotoxic T cells to CD19 + target B cells of ALL inducing their serial lysis. Areas covered: This review focuses on the efficacy and safety of blinatumomab used for the treatment of relapsed/refractory (R/R) ALL and minimal residual disease (MRD)-positive B-cell precursor (BCP) ALL in adults and children, as well as the future prospects of this drug in the treatment of ALL. Expert commentary: Blinatumomab has demonstrated encouraging response rates in MRD-positive and R/R in adults with Philadelphia chromosome-positive and -negative ALL, as well as in children with R/R ALL. Blinatumomab has a favorable safety profile, although reversible CNS events and cytokine release syndrome can occur. Ongoing trials in ALL incorporate blinatumomab in the first line therapy of BCP ALL in combination with chemotherapy, targeted therapies or other immunotherapies with the aim of increasing the depth of the remission and decreasing the probability of relapse.

Intermittent theta-burst transcranial magnetic stimulation for autism spectrum disorder: an open-label pilot study.

PubMed

Abujadi, Caio; Croarkin, Paul E; Bellini, Bianca B; Brentani, Helena; Marcolin, Marco A

2017-12-11

Theta-burst stimulation (TBS) modulates synaptic plasticity more efficiently than standard repetitive transcranial magnetic stimulation delivery and may be a promising modality for neuropsychiatric disorders such as autism spectrum disorder (ASD). At present there are few effective interventions for prefrontal cortex dysfunction in ASD. We report on an open-label, pilot study of intermittent TBS (iTBS) to target executive function deficits and restricted, repetitive behaviors in male children and adolescents with ASD. Ten right-handed, male participants, aged 9-17 years with ASD were enrolled in an open-label trial of iTBS treatment. Fifteen sessions of neuronavigated iTBS at 100% motor threshold targeting the right dorsolateral prefrontal cortex were delivered over 3 weeks. Parent report scores on the Repetitive Behavior Scale Revised and the Yale-Brown Obsessive Compulsive Scale demonstrated improvements with iTBS treatment. Participants demonstrated improvements in perseverative errors on the Wisconsin Card Sorting Test and total time for the Stroop test. The iTBS treatments were well tolerated with no serious adverse effects. These preliminary results suggest that further controlled interventional studies of iTBS for ASD are warranted.

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

PubMed Central

Bhuvaneswari, Ramaswamy; Gan, Yik Yuen; Soo, Khee Chee; Olivo, Malini

2009-01-01

Background Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period. Results Our results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux. Conclusion The combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors. PMID:19878607

Novel methotrexate soft nanocarrier/fractional erbium YAG laser combination for clinical treatment of plaque psoriasis.

PubMed

Ramez, Shahenda A; Soliman, Mona M; Fadel, Maha; Nour El-Deen, Faisal; Nasr, Maha; Youness, Eman R; Aboel-Fadl, Dalea M

2018-02-15

Psoriasis is a commonly encountered chronic dermatological disease, presenting with inflammatory symptoms in patients. Systemic treatment of psoriasis is associated with several adverse effects, therefore the development of a customized topical treatment modality for psoriasis would be an interesting alternative to systemic delivery. The therapeutic modality explored in this article was the comparative treatment of psoriatic patients using nanoparticulated methotrexate in the form of jojoba oil-based microemulsion with or without fractional erbium YAG laser. Assessment parameters included follow-up photography for up to 8 weeks of treatment, estimation of the psoriasis severity [TES (thickness, erythema, scales)] score, and histopathological skin evaluation. The prepared methotrexate microemulsion was clinically beneficial and safe in treatment of psoriasis vulgaris. The concomitant use of the fractional laser provided improvement in the psoriatic plaques within shorter time duration (3 weeks compared to 8 weeks of treatment), presenting an alternative topical treatment modality for psoriasis vulgaris.

The Function of Consciousness in Multisensory Integration

ERIC Educational Resources Information Center

Palmer, Terry D.; Ramsey, Ashley K.

2012-01-01

The function of consciousness was explored in two contexts of audio-visual speech, cross-modal visual attention guidance and McGurk cross-modal integration. Experiments 1, 2, and 3 utilized a novel cueing paradigm in which two different flash suppressed lip-streams cooccured with speech sounds matching one of these streams. A visual target was…

Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices.

PubMed

Zhao, Chan; Zhang, Meifen

2017-04-10

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness, which are believed to be the two most important factors affecting treatment decision making.

Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

PubMed

Weber, Damien C; Bogner, Joachim; Verwey, Jorn; Georg, Dietmar; Dieckmann, Karin; Escudé, Lluis; Caro, Monica; Pötter, Richard; Goitein, Gudrun; Lomax, Antony J; Miralbell, Raymond

2005-10-01

A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. Target coverage of all simulated uveal melanomas was equally conformal with the photon and proton modalities. The median CI(95%) value was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans, respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS and substantially improved with IMPT in some tumor cases (median CI(95%), 1.29). The tumor dose homogeneity in the proton plans was, however, always better than with SRT photon planning (median inhomogeneity coefficient 0.1 and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static, dynamic, and IMSRT plans, respectively). Compared with the photon plans, the use of protons did not lead to a substantial reduction in the homolateral OAR total integral dose in the low- to high-dose level, except for the lacrimal gland. The median maximal dose and dose at the 10% volume with the static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy, respectively, for the lacrimal gland, a critical organ. For protons, only the OPTIS plans were better, with a median maximal dose and dose at the 10% volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE, respectively. The contralateral OARs were completely spared with the proton plans, but the median dose delivered to these structures was 1.2 Gy (range, 0-6.3 Gy) with the SRT photon plans. These results suggest that the use of SRT photon techniques, compared with protons, can result in similar levels of dose conformation. IMPT did not increase the degree of conformality for this small tumor. Tumor dose inhomogeneity was, however, always increased with photon planning. Except for the lacrimal gland, the use of protons, with or without intensity modulation, did not increase homolateral OAR dose sparing. The dose to all the contralateral OARs was, however, completely eliminated with proton planning.

Ego mechanisms of defense are associated with patients' preference of treatment modality independent of psychological distress in end-stage renal disease.

PubMed

Hyphantis, Thomas; Katsoudas, Spiros; Voudiclari, Sonia

2010-03-24

Several parameters mediate the selection of treatment modality in end-stage renal disease (ESRD). The nephrology community suggests that patient preference should be the prime determinant of modality choice. We aimed to test whether ego mechanisms of defense are associated with patients' treatment modality preferences, independent of psychological distress. In 58 eligible ESRD patients who had themselves chosen their treatment modality, we administered the Symptom Distress Checklist-90-R and the Defense Style Questionnaire. Thirty-seven patients (53.4%) had chosen hemodialysis and 21 (46.6%) peritoneal dialysis. Patients who preferred peritoneal dialysis were younger (odds ratio [OR], 0.89; 95% confidence interval [CI]: 0.804-0.988), had received more education (OR, 8.84; 95% CI: 1.301-60.161), and were twice as likely to adopt an adaptive defense style as compared to patients who preferred hemodialysis (57.1% vs 27.0%, respectively; P < 0.033). On the contrary, the latter were more likely to adopt an image-distorting defense style (35.1% vs 14.3%; P = 0.038) and passive-aggressive defenses (OR, 0.73: 95% CI: 0.504-1.006). These results were independent of psychological distress. Our findings indicate that the patient's personality should be taken into account, if we are to better define which modalities are best suited to which patients. Also, physicians should bear in mind passive-aggressive behaviors that warrant attention and intervention in patients who preferred hemodialysis.

Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities.

PubMed

Prens, Sebastiaan P; de Vries, Karin; Neumann, H A Martino; Prens, Errol P

2013-06-01

Actinic keratoses (AK) are premalignant lesions occurring mainly in sun-damaged skin. Current topical treatment options for AK and photo-damaged skin such as liquid nitrogen and electrosurgery are not suitable for field treatment. Otherwise, therapies suitable for field treatment bring along considerable patient discomfort. Non-ablative fractional resurfacing has emerged as a logical treatment option especially for field treatment of AK. To evaluate the clinical efficacy of fractional laser therapy for clearing AK and improving skin quality. To compare patient friendliness of the "fractional" therapy with those reported for other field treatment modalities. Ten patients with Fitzpatrick skin type I to III with multiple AK and extensive sun-damaged skin, received 5-10 sessions with a 4-week interval using a 1550 nm Erbium-Glass Fractionated laser (Sellas, Korea). Four weeks and 24 weeks after the last treatment the clinical results were evaluated by an independent physician. The mean degree of improvement, in terms of reduction in the number of AK and improvement of skin texture, was 54% on a 4 point PGA scale, and persisted for approximately 6 months. The biggest advantage of fractional laser treatment, besides the eradication of AK and a clear rejuvenation effect, is the absence of "downtime". Fractional non-ablative resurfacing induces significant reduction in the number of AK and improves the skin quality. Also all patients preferred fractional laser therapy above other AK treatment modalities.

Wilderness Therapy: Ethical Considerations for Mental Health Professionals

ERIC Educational Resources Information Center

Becker, Stephen P.

2010-01-01

Wilderness therapy is a growing treatment modality for adolescents presenting with a variety of clinical concerns, and wilderness therapy clinicians and referring mental health professionals must carefully consider the ethical issues that are unique to this modality. Following an overview of wilderness therapy as a mental health treatment,…

Alcoholism treatment and medical care costs from Project MATCH.

PubMed

Holder, H D; Cisler, R A; Longabaugh, R; Stout, R L; Treno, A J; Zweben, A

2000-07-01

This paper examines the costs of medical care prior to and following initiation of alcoholism treatment as part of a study of patient matching to treatment modality. Longitudinal study with pre- and post-treatment initiation. The total medical care costs for inpatient and outpatient treatment for patients participating over a span of 3 years post-treatment. Three treatment sites at two of the nine Project MATCH locations (Milwaukee, WI and Providence, RI). Two hundred and seventy-nine patients. Patients were randomly assigned to one of three treatment modalities: a 12-session cognitive behavioral therapy (CBT), a four-session motivational enhancement therapy (MET) or a 12-session Twelve-Step facilitation (TSF) treatment over 12 weeks. Total medical care costs declined from pre- to post-treatment overall and for each modality. Matching effects independent of clinical prognosis showed that MET has potential for medical-care cost-savings. However, patients with poor prognostic characteristics (alcohol dependence, psychiatric severity and/or social network support for drinking) have better cost-savings potential with CBT and/or TSF. Matching variables have significant importance in increasing the potential for medical-care cost-reductions following alcoholism treatment.

Emerging drugs for coeliac disease.

PubMed

Mooney, Peter D; Hadjivassiliou, Marios; Sanders, David S

2014-12-01

Coeliac disease is an autoimmune gluten sensitive enteropathy and is now known to affect 1% of the adult population. A gluten-free diet (GFD) should be curative; however, up to 30% of patients have persistent symptoms and many patients find the diet difficult to fully adhere to. Currently, there are no licensed therapeutic options for patients with coeliac disease outside of a GFD. This review will outline the case for alternative treatments and discuss the potential therapeutic targets. The products in the most advanced stage of development will be discussed in detail. There is clearly an unmet need for alternatives to a GFD for the treatment of coeliac disease. Oral glutenase supplements to improve the degradation of gluten into non-toxic peptides appear to be the most likely to provide a breakthrough in the treatment of coeliac disease; however, other modalities such as a therapeutic vaccine or zonulin inhibitors to reduce intestinal permeability have shown promising results.

Turning the gene tap off; implications of regulating gene expression for cancer therapeutics

PubMed Central

Curtin, James F.; Candolfi, Marianela; Xiong, Weidong; Lowenstein, Pedro R.; Castro, Maria G.

2008-01-01

Cancer poses a tremendous therapeutic challenge worldwide, highlighting the critical need for developing novel therapeutics. A promising cancer treatment modality is gene therapy, which is a form of molecular medicine designed to introduce into target cells genetic material with therapeutic intent. Anticancer gene therapy strategies currently used in preclinical models, and in some cases in the clinic, include proapoptotic genes, oncolytic/replicative vectors, conditional cytotoxic approaches, inhibition of angiogenesis, inhibition of growth factor signaling, inactivation of oncogenes, inhibition of tumor invasion and stimulation of the immune system. The translation of these novel therapeutic modalities from the preclinical setting to the clinic has been driven by encouraging preclinical efficacy data and advances in gene delivery technologies. One area of intense research involves the ability to accurately regulate the levels of therapeutic gene expression to achieve enhanced efficacy and provide the capability to switch gene expression off completely if adverse side effects should arise. This feature could also be implemented to switch gene expression off when a successful therapeutic outcome ensues. Here, we will review recent developments related to the engineering of transcriptional switches within gene delivery systems, which could be implemented in clinical gene therapy applications directed at the treatment of cancer. PMID:18347132

Expected Paradigm Shift in Brain Metastases Therapy-Immune Checkpoint Inhibitors.

PubMed

Jindal, Vishal; Gupta, Sorab

2018-01-30

Brain metastasis (BM) is one of the dreadful complications of malignancies. The prognosis after BM is extremely poor and life expectancy is meager. Currently, our treatment modalities are limited to radiotherapy and surgical resection, which also has poor outcomes and leads to various neurological deficits and affects the quality of life of patients. New treatment modality, i.e., immune checkpoint inhibitors, has brought revolution in management of melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors basically enhance the immune response of the body to fight against cancers. Immune response in the brain is highly regulated; therefore, it is challenging to use immune-modulator drugs in BM. The microenvironment of BM is rich in cytotoxic T lymphocytes and which is the target of immune checkpoint inhibitors. Few studies have shown some hope regarding use of immune checkpoint inhibitors in management of BM. It works through inhibiting immune check point gates, i.e., CTLA-4 (cytotoxic T-lymphocyte-associated protein) and PD-1/PD-L1 (programmed cell death protein-1/program death ligand-1). This article explains the basic mechanism of immune check point inhibitors, rationale behind their usage in BM, and some of the clinical studies which have shown the efficacy of immune check point inhibitors in BM.

MO-E-BRD-01: Is Non-Invasive Image-Guided Breast Brachytherapy Good?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiatt, J.

2015-06-15

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

Interstitial devices for treating deep seated tumors

NASA Astrophysics Data System (ADS)

Lafon, Cyril; Cathignol, Dominique; Prat, Frédéric; Melodelima, David; Salomir, Rares; Theillère, Yves; Chapelon, Jean-Yves

2006-05-01

Techniques using intracavitary or interstitial applicators have been proposed because extracorporeal HIFU techniques are not always suitable for deep-seated tumors. Bones or gaseous pockets may indeed be located in the intervening tissue. The objective is to bring the ultrasound source as close as possible to the target through natural routes in order to minimize the effects of attenuation and phase aberration along the ultrasound pathway. Under these circumstances, it becomes possible to use higher frequency, thus increasing the ultrasonic absorption coefficient and resulting in more efficient heating of the treatment region. In contrast to extra-corporeal applicators, the design of interstitial probes imposes additional constraints relative to size and ergonomy. The goal of this paper is to present the range of miniature interstitial applicators we developed at INSERM for various applications. The sources are rotating plane water-cooled transducers that operate at a frequency between 3 and 10 MHz depending on the desired therapeutic depth. The choice of a plane transducer rather than divergent sources permits to extend the therapeutic depth and to enhance the angular selectivity of the treatment Rotating single element flat transducer can also be replaced by cylindrical arrays for rotating electronically a reconstructed plane wave. When extended zone of coagulation are required, original therapeutic modalities combining cavitation and thermal effects are used. These methods consist in favoring in depth heating by increasing the acoustic attenuation away from the transducer with the presence of bubbles. When associated to modern imaging modalities, these minimally invasive therapeutic devices offer very promising options for cancer treatment. For examples, two versions of an image-guided esophageal applicator are designed: one uses a retractable ultrasound mini probe for the positioning of the applicator, while the other is MRI compatible and offers on line monitoring of temperature. Beyond these engineering considerations, our clinical experience demonstrates that following interstitial routes for applying HIFU is an interesting therapeutic option when targeted sites cannot be reached from outside the patient.

MO-E-BRD-03: Intra-Operative Breast Brachytherapy: Is One Stop Shopping Best? [Non-invasive Image-Guided Breast Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Libby, B.

2015-06-15

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

MO-E-BRD-02: Accelerated Partial Breast Irradiation in Brachytherapy: Is Shorter Better?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todor, D.

2015-06-15

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

WE-AB-207B-07: Dose Cloud: Generating “Big Data” for Radiation Therapy Treatment Plan Optimization Research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Folkerts, MM; University of California San Diego, La Jolla, California; Long, T

Purpose: To provide a tool to generate large sets of realistic virtual patient geometries and beamlet doses for treatment optimization research. This tool enables countless studies exploring the fundamental interplay between patient geometry, objective functions, weight selections, and achievable dose distributions for various algorithms and modalities. Methods: Generating realistic virtual patient geometries requires a small set of real patient data. We developed a normalized patient shape model (PSM) which captures organ and target contours in a correspondence-preserving manner. Using PSM-processed data, we perform principal component analysis (PCA) to extract major modes of variation from the population. These PCA modes canmore » be shared without exposing patient information. The modes are re-combined with different weights to produce sets of realistic virtual patient contours. Because virtual patients lack imaging information, we developed a shape-based dose calculation (SBD) relying on the assumption that the region inside the body contour is water. SBD utilizes a 2D fluence-convolved scatter kernel, derived from Monte Carlo simulations, and can compute both full dose for a given set of fluence maps, or produce a dose matrix (dose per fluence pixel) for many modalities. Combining the shape model with SBD provides the data needed for treatment plan optimization research. Results: We used PSM to capture organ and target contours for 96 prostate cases, extracted the first 20 PCA modes, and generated 2048 virtual patient shapes by randomly sampling mode scores. Nearly half of the shapes were thrown out for failing anatomical checks, the remaining 1124 were used in computing dose matrices via SBD and a standard 7-beam protocol. As a proof of concept, and to generate data for later study, we performed fluence map optimization emphasizing PTV coverage. Conclusions: We successfully developed and tested a tool for creating customizable sets of virtual patients suitable for large-scale radiation therapy optimization research.« less

Update on Postsurgical Scar Management

PubMed Central

Commander, Sarah Jane; Chamata, Edward; Cox, Joshua; Dickey, Ryan M.; Lee, Edward I.

2016-01-01

Postoperative scar appearance is often a significant concern among patients, with many seeking advice from their surgeons regarding scar minimization. Numerous products are available that claim to decrease postoperative scar formation and improve wound healing. These products attempt to create an ideal environment for wound healing by targeting the three phases of wound healing: inflammation, proliferation, and remodeling. With that said, preoperative interventions, such as lifestyle modifications and optimization of medical comorbidities, and intraoperative interventions, such as adherence to meticulous operative techniques, are equally important for ideal scarring. In this article, the authors review the available options in postoperative scar management, addressing the benefits of multimodal perioperative intervention. Although numerous treatments exist, no single modality has been proven superior over others. Therefore, each patient should receive a personalized treatment regimen to optimize scar management. PMID:27478420

Genetics and Genomics of Acute Neurologic Disorders.

PubMed

Maserati, Megan; Alexander, Sheila A

2018-01-01

Neurologic diseases and injuries are complex and multifactorial, making risk prediction, targeted treatment modalities, and outcome prognostication difficult and elusive. Genetics and genomics have affected clinical practice in many aspects in medicine, particularly cancer treatment. Advancements in knowledge of genetic and genomic variability in neurologic disease and injury are growing rapidly. Although these data are not yet ready for use in clinical practice, research continues to progress and elucidate information that eventually will provide answers to complex neurologic questions and serve as a platform to provide individualized care plans aimed at improving outcomes. This article provides a focused review of relevant literature on genetics, genomics, and common complex neurologic disease and injury likely to be seen in the acute care setting. ©2018 American Association of Critical-Care Nurses.

Fractional 532-nm Q-switched Nd:YAG laser: One of the safest novel treatment modality to treat café-au-lait macules.

PubMed

Won, Kwang Hee; Lee, Ye Jin; Rhee, Do Young; Chang, Sung Eun

2016-10-01

Café-au-lait macules (CALMs) are benign epidermal basilar hyperpigmentations that can be found in an isolated form or in association with neurocutaneous syndromes. Frequency-doubled Q-switched neodymium-doped yttrium aluminum garnet laser (532-nm QSNYL) does not penetrate deeply into the skin and is therefore suitable for epidermal pigmented lesion. Fractional photothermolysis (FP) targets only very small areas of the skin, without injuring adjacent areas of healthy, normal skin. Herein, we report a case of CALMs successfully treated with fractional 532-nm QSNYL. By applying FP to 532-nm QSNYL, we could treat CALMs safely with less downtime as compared to conventional laser treatments and expect more energy delivery for each microscopic hole, thereby allowing higher response rate.

Do skeletal muscle properties recover following repeat onabotulinum toxin A injections?

PubMed

Fortuna, Rafael; Horisberger, Monika; Vaz, Marco Aurélio; Herzog, Walter

2013-09-27

Onabotulinum toxin A (BTX-A) is a frequently used treatment modality to relax spastic muscles by preventing acetylcholine release at the motor nerve endings. Although considered safe, previous studies have shown that BTX-A injections cause muscle atrophy and deterioration in target and non-target muscles. Ideally, muscles should fully recover following BTX-A treatments, so that muscle strength and performance are not affected in the long-term. However, systematic, long-term data on the recovery of muscles exposed to BTX-A treatments are not available, thus practice guidelines on the frequency and duration of BTX-A injections, and associated recovery protocols, are based on clinical experience with little evidence-based information. Therefore, the purpose of this study was to investigate muscle recovery following a six months, monthly BTX-A injection (3.5 U/kg) protocol. Twenty seven skeletally mature NZW rabbits were divided into 5 groups: Control (n=5), zero month recovery - BTX-A+0M (n=5), one month recovery - BTX-A+1M (n=5), three months recovery - BTX-A+3M (n=5), and six months recovery - BTX-A+6M (n=7). Knee extensor strength, muscle mass and percent contractile material in injected and contralateral non-injected muscles was measured at each point of recovery. Strength and muscle mass were partially and completely recovered in injected and contralateral non-injected muscles for BTX-A+6M group animals, respectively. The percent of contractile material partially recovered in the injected, but did not recover in the contralateral non-injected muscles. We conclude from these results that neither target nor non-target muscles fully recover within six months of a BTX-A treatment protocol and that clinical studies on muscle recovery should be pursued. © 2013 Elsevier Ltd. All rights reserved.

Analysis of the costs of dialysis and the effects of an incentive mechanism for low-cost dialysis modalities.

PubMed

Cleemput, Irina; De Laet, Chris

2013-05-01

Treatment costs of end-stage renal disease with dialysis are high and vary between dialysis modalities. Public healthcare payers aim at stimulating the use of less expensive dialysis modalities, with maintenance of healthcare quality. This study examines the effects of Belgian financial incentive mechanisms for the use of low-cost dialysis treatments. First, the costs of different dialysis modalities were calculated from the hospital's perspective. Data were obtained through a hospital survey. The balance between costs and revenues was simulated for an average Belgian dialysis programme. Incremental profits were calculated in function of the proportion of patients on alternative dialysis modalities. Hospital haemodialysis is the most expensive modality per patient year, followed by peritoneal dialysis and finally satellite haemodialysis. Under current reimbursement rules mean profits of a dialysis programme are maximal if about 28% of patients are treated with a low-cost dialysis modality. This is only slightly lower than the observed percentage in Belgian dialysis centres in the same period. In Belgium, the financial incentives for the use of low-cost dialysis modalities only had a modest impact due to the continuing profits that could be generated by high-cost dialysis. Profit neutrality is crucial for the success of any financial incentive mechanism for low-cost dialysis modalities. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

PET/CT image registration: preliminary tests for its application to clinical dosimetry in radiotherapy.

PubMed

Baños-Capilla, M C; García, M A; Bea, J; Pla, C; Larrea, L; López, E

2007-06-01

The quality of dosimetry in radiotherapy treatment requires the accurate delimitation of the gross tumor volume. This can be achieved by complementing the anatomical detail provided by CT images through fusion with other imaging modalities that provide additional metabolic and physiological information. Therefore, use of multiple imaging modalities for radiotherapy treatment planning requires an accurate image registration method. This work describes tests carried out on a Discovery LS positron emission/computed tomography (PET/CT) system by General Electric Medical Systems (GEMS), for its later use to obtain images to delimit the target in radiotherapy treatment. Several phantoms have been used to verify image correlation, in combination with fiducial markers, which were used as a system of external landmarks. We analyzed the geometrical accuracy of two different fusion methods with the images obtained with these phantoms. We first studied the fusion method used by the PET/CT system by GEMS (hardware fusion) on the basis that there is satisfactory coincidence between the reconstruction centers in CT and PET systems; and secondly the fiducial fusion, a registration method, by means of least-squares fitting algorithm of a landmark points system. The study concluded with the verification of the centroid position of some phantom components in both imaging modalities. Centroids were estimated through a calculation similar to center-of-mass, weighted by the value of the CT number and the uptake intensity in PET. The mean deviations found for the hardware fusion method were: deltax/ +/-sigma = 3.3 mm +/- 1.0 mm and /deltax/ +/-sigma = 3.6 mm +/- 1.0 mm. These values were substantially improved upon applying fiducial fusion based on external landmark points: /deltax/ +/-sigma = 0.7 mm +/- 0.8 mm and /deltax/ +/-sigma = 0.3 mm 1.7 mm. We also noted that differences found for each of the fusion methods were similar for both the axial and helical CT image acquisition protocols.

Intravital imaging of mouse colonic adenoma using MMP-based molecular probes with multi-channel fluorescence endoscopy.

PubMed

Oh, Gyungseok; Yoo, Su Woong; Jung, Yebin; Ryu, Yeon-Mi; Park, Youngrong; Kim, Sang-Yeob; Kim, Ki Hean; Kim, Sungjee; Myung, Seung-Jae; Chung, Euiheon

2014-05-01

Intravital imaging has provided molecular, cellular and anatomical insight into the study of tumor. Early detection and treatment of gastrointestinal (GI) diseases can be enhanced with specific molecular markers and endoscopic imaging modalities. We present a wide-field multi-channel fluorescence endoscope to screen GI tract for colon cancer using multiple molecular probes targeting matrix metalloproteinases (MMP) conjugated with quantum dots (QD) in AOM/DSS mouse model. MMP9 and MMP14 antibody (Ab)-QD conjugates demonstrate specific binding to colonic adenoma. The average target-to-background (T/B) ratios are 2.10 ± 0.28 and 1.78 ± 0.18 for MMP14 Ab-QD and MMP9 Ab-QD, respectively. The overlap between the two molecular probes is 67.7 ± 8.4%. The presence of false negative indicates that even more number of targeting could increase the sensitivity of overall detection given heterogeneous molecular expression in tumors. Our approach indicates potential for the screening of small or flat lesions that are precancerous.

Application of the dual-component model of working memory to ADHD:Greater secondary memory deficit despite confounded cognitive differences.

PubMed

Gibson, Bradley S; Gondoli, Dawn M; Ralph, Kathryn J; Sztybel, Pedro

2018-01-01

The dual-component model postulates that working memory capacity consists of two dissociable components: maintenance in primary memory (PM) and retrieval from secondary memory (SM). Recent application of this model to attention-deficit/hyperactivity disorder (ADHD) has revealed that the SM component is more deficient than the PM component across both verbal and spatial modalities. The present study attempts to strengthen this conclusion by addressing two weaknesses in the previous study. First, the present study shows that the SM component continues to be more deficient than the PM component across both modalities under conditions in which (1) all participants were instructed to use the same recall strategy (resulting in the exclusion of fewer participants); and, (2) individual differences in this strategy were controlled. Second, the present study also documents a group difference in word reading efficiency that is confounded with diagnostic status and that might have influenced estimates of PM and SM capacities in the verbal modality. However, although the SM component is more deficient than the PM component in the ADHD group, the magnitude of this interaction does not vary as a function task modality. These findings are interpreted to suggest that the pattern of WM deficiencies observed are part of a causal pathway that can lead to the symptoms of ADHD, as well as to impairments in reading (and intelligence) due to overlapping cue-dependent retrieval mechanisms. These findings provide additional support for the notion that the SM component of WM is an important and neglected target for treatment.

Characterization of an elastic target in a shallow water waveguide by decomposition of the time-reversal operator.

PubMed

Philippe, Franck D; Prada, Claire; de Rosny, Julien; Clorennec, Dominique; Minonzio, Jean-Gabriel; Fink, Mathias

2008-08-01

This paper reports the results of an investigation into extracting of the backscattered frequency signature of a target in a waveguide. Retrieving the target signature is difficult because it is blurred by waveguide reflections and modal interference. It is shown that the decomposition of the time-reversal operator method provides a solution to this problem. Using a modal theory, this paper shows that the first singular value associated with a target is proportional to the backscattering form function. It is linked to the waveguide geometry through a factor that weakly depends on frequency as long as the target is far from the boundaries. Using the same approach, the second singular value is shown to be proportional to the second derivative of the angular form function which is a relevant parameter for target identification. Within this framework the coupling between two targets is considered. Small scale experimental studies are performed in the 3.5 MHz frequency range for 3 mm spheres in a 28 mm deep and 570 mm long waveguide and confirm the theoretical results.

Haptic guidance of overt visual attention.

PubMed

List, Alexandra; Iordanescu, Lucica; Grabowecky, Marcia; Suzuki, Satoru

2014-11-01

Research has shown that information accessed from one sensory modality can influence perceptual and attentional processes in another modality. Here, we demonstrated a novel crossmodal influence of haptic-shape information on visual attention. Participants visually searched for a target object (e.g., an orange) presented among distractor objects, fixating the target as quickly as possible. While searching for the target, participants held (never viewed and out of sight) an item of a specific shape in their hands. In two experiments, we demonstrated that the time for the eyes to reach a target-a measure of overt visual attention-was reduced when the shape of the held item (e.g., a sphere) was consistent with the shape of the visual target (e.g., an orange), relative to when the held shape was unrelated to the target (e.g., a hockey puck) or when no shape was held. This haptic-to-visual facilitation occurred despite the fact that the held shapes were not predictive of the visual targets' shapes, suggesting that the crossmodal influence occurred automatically, reflecting shape-specific haptic guidance of overt visual attention.

Ground Vibration Test Planning and Pre-Test Analysis for the X-33 Vehicle

NASA Technical Reports Server (NTRS)

Bedrossian, Herand; Tinker, Michael L.; Hidalgo, Homero

2000-01-01

This paper describes the results of the modal test planning and the pre-test analysis for the X-33 vehicle. The pre-test analysis included the selection of the target modes, selection of the sensor and shaker locations and the development of an accurate Test Analysis Model (TAM). For target mode selection, four techniques were considered, one based on the Modal Cost technique, one based on Balanced Singular Value technique, a technique known as the Root Sum Squared (RSS) method, and a Modal Kinetic Energy (MKE) approach. For selecting sensor locations, four techniques were also considered; one based on the Weighted Average Kinetic Energy (WAKE), one based on Guyan Reduction (GR), one emphasizing engineering judgment, and one based on an optimum sensor selection technique using Genetic Algorithm (GA) search technique combined with a criteria based on Hankel Singular Values (HSV's). For selecting shaker locations, four techniques were also considered; one based on the Weighted Average Driving Point Residue (WADPR), one based on engineering judgment and accessibility considerations, a frequency response method, and an optimum shaker location selection based on a GA search technique combined with a criteria based on HSV's. To evaluate the effectiveness of the proposed sensor and shaker locations for exciting the target modes, extensive numerical simulations were performed. Multivariate Mode Indicator Function (MMIF) was used to evaluate the effectiveness of each sensor & shaker set with respect to modal parameter identification. Several TAM reduction techniques were considered including, Guyan, IRS, Modal, and Hybrid. Based on a pre-test cross-orthogonality checks using various reduction techniques, a Hybrid TAM reduction technique was selected and was used for all three vehicle fuel level configurations.

A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries.

PubMed

Liu, Liang Qin; Moody, Julie; Traynor, Michael; Dyson, Sue; Gall, Angela

2014-11-01

Electrical stimulation (ES) can confer benefit to pressure ulcer (PU) prevention and treatment in spinal cord injuries (SCIs). However, clinical guidelines regarding the use of ES for PU management in SCI remain limited. To critically appraise and synthesize the research evidence on ES for PU prevention and treatment in SCI. Review was limited to peer-reviewed studies published in English from 1970 to July 2013. Studies included randomized controlled trials (RCTs), non-RCTs, prospective cohort studies, case series, case control, and case report studies. Target population included adults with SCI. Interventions of any type of ES were accepted. Any outcome measuring effectiveness of PU prevention and treatment was included. Methodological quality was evaluated using established instruments. Twenty-seven studies were included, 9 of 27 studies were RCTs. Six RCTs were therapeutic trials. ES enhanced PU healing in all 11 therapeutic studies. Two types of ES modalities were identified in therapeutic studies (surface electrodes, anal probe), four types of modalities in preventive studies (surface electrodes, ES shorts, sacral anterior nerve root implant, neuromuscular ES implant). The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations, and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters, and conduct more rigorous trials.

A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries

PubMed Central

Liu, Liang Qin; Moody, Julie; Traynor, Michael; Dyson, Sue; Gall, Angela

2014-01-01

Context Electrical stimulation (ES) can confer benefit to pressure ulcer (PU) prevention and treatment in spinal cord injuries (SCIs). However, clinical guidelines regarding the use of ES for PU management in SCI remain limited. Objectives To critically appraise and synthesize the research evidence on ES for PU prevention and treatment in SCI. Method Review was limited to peer-reviewed studies published in English from 1970 to July 2013. Studies included randomized controlled trials (RCTs), non-RCTs, prospective cohort studies, case series, case control, and case report studies. Target population included adults with SCI. Interventions of any type of ES were accepted. Any outcome measuring effectiveness of PU prevention and treatment was included. Methodological quality was evaluated using established instruments. Results Twenty-seven studies were included, 9 of 27 studies were RCTs. Six RCTs were therapeutic trials. ES enhanced PU healing in all 11 therapeutic studies. Two types of ES modalities were identified in therapeutic studies (surface electrodes, anal probe), four types of modalities in preventive studies (surface electrodes, ES shorts, sacral anterior nerve root implant, neuromuscular ES implant). Conclusion The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations, and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters, and conduct more rigorous trials. PMID:24969965

New perspectives in the treatment of Cushing's syndrome.

PubMed

Labeur, M; Arzt, E; Stalla, G K; Páez-Pereda, M

2004-12-01

Regardless of etiology, all cases of endogenous Cushing's syndrome are due to increased production of cortisol by the adrenal gland. Most are caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas. Alternatively, the glucocorticoid excess may be due to adrenal neoplasia or to ectopic ACTH-secreting tumors. Cushing's syndrome is characterized by endocrine and metabolic alterations such as truncal obesity, hypertension, weakness, amenorrhea, hyperglycemia, osteoporosis and depression. Unless treated, the disease is associated with high morbidity, and ultimately, mortality. Depending on the etiology of Cushing's syndrome two different treatment modalities are possible: reduction of pituitary ACTH production or reduction of adrenocortical cortisol secretion. In the absence of efficient drug therapy, transsphenoidal resection of the pituitary adenoma is the primary treatment of choice for the reduction of ACTH secretion. In the last years there was much progress in understanding the molecular mechanisms that control the function of the hypothalamic-pituitary-adrenal axis. Thus, new insights made it possible to identify potential drug targets for the treatment of Cushing's syndrome. The present article reviews different drug targets and therapeutic options including drugs that control the central ACTH regulation, e.g. by modulating signaling pathways and transcriptional regulation of ACTH biosynthesis, corticotrophin releasing hormone (CRH) or glucocorticoid receptor antagonists, inhibitors of glucocorticoid synthesis, ketoconazole, somatostatin and dopamine analogs. Some of these substances might be useful for the treatment of Cushing's syndrome.

Neuroimaging in ophthalmology

PubMed Central

Kim, James D.; Hashemi, Nafiseh; Gelman, Rachel; Lee, Andrew G.

2012-01-01

In the past three decades, there have been countless advances in imaging modalities that have revolutionized evaluation, management, and treatment of neuro-ophthalmic disorders. Non-invasive approaches for early detection and monitoring of treatments have decreased morbidity and mortality. Understanding of basic methods of imaging techniques and choice of imaging modalities in cases encountered in neuro-ophthalmology clinic is critical for proper evaluation of patients. Two main imaging modalities that are often used are computed tomography (CT) and magnetic resonance imaging (MRI). However, variations of these modalities and appropriate location of imaging must be considered in each clinical scenario. In this article, we review and summarize the best neuroimaging studies for specific neuro-ophthalmic indications and the diagnostic radiographic findings for important clinical entities. PMID:23961025

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bazalova, Magdalena, E-mail: bazalova@stanford.edu; Nelson, Geoff; Noll, John M.

Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approaches—a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCTmore » scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. Conclusions: The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.« less

Technological advances in the surgical treatment of movement disorders.

PubMed

Gross, Robert E; McDougal, Margaret E

2013-08-01

Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in inserting neuromodulation modalities, including DBS, to the target, and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength magnetic resonance imaging and other innovations, such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable computed tomography scanners also are facilitating lead implantation without monitoring, as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue and, in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system, reflected in biomarkers continuously recorded by the devices. Finer-grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via current steering algorithms. Finally, even thermocoagulation-essentially replaced by DBS-is being advanced by new minimally-invasive approaches that may improve this therapy for selected patients in whom it may be preferred. Functional neurosurgery has a history of being driven by technological innovation, a tradition that continues into its future.

A multifunctional poly(curcumin) nanomedicine for dual-modal targeted delivery, intracellular responsive release, dual-drug treatment and imaging of multidrug resistant cancer cells† †Electronic supplementary information (ESI) available: The synthesis procedure of Biotin–PEG–PCDA and the experimental results of MTT. See DOI: 10.1039/c5tb02450a Click here for additional data file.

PubMed Central

Wang, Jining; Wang, Feihu; Li, Fangzhou; Zhang, Wenjun

2016-01-01

A multifunctional anti-cancer nanomedicine based on a biotin–poly(ethylene glycol)–poly(curcumin-dithio dipropionic acid) (Biotin–PEG–PCDA) polymeric nanocarrier loaded with paclitaxel (PTX), magnetic nanoparticles (MNPs) and quantum dots (QDs) is developed. It combines advantageous properties of efficient targeted delivery and uptake (via biotin and MNP), intracellular responsive release (via cleavable PCDA polymer), fluorescence imaging (via QD) and combined PTX-curcumin dual-drug treatment, allowing for overcoming drug resistance mechanisms of model multidrug resistant breast cancer cells (MCF-7/ADR). The PTX/MNPs/QDs@Biotin–PEG–PCDA nanoparticles are highly stable under physiological conditions, but are quickly disassembled to release their drug load in the presence of 10 mM glutathione (GSH). The nanoparticles show high uptake by tumour cells from a combined effect of magnet targeting and biotin receptor-mediated internalization. Moreover, curcumin, an intracellularly cleaved product of PCDA, can effectively down regulate the expression of drug efflux transporters such as P-glycoprotein (P-gp) to increase PTX accumulation within target cancer cells, thereby enhancing PTX induced cytotoxicity and therapeutic efficacy against MCF-7/ADR cells. Taken together, this novel tumour-targeting and traceable multifunctional nanomedicine is highly effective against model MDR cancer at the cellular level. PMID:27152196

Individual and group sensitivity to remedial reading program design: Examining reading gains across three middle school reading projects

PubMed Central

Calhoon, Mary Beth; Petscher, Yaacov

2015-01-01

The purpose of this project was to examine group- and individual-level responses by struggling adolescents readers (6th – 8th grades; N = 155) to three different modalities of the same reading program, Reading Achievement Multi-Component Program (RAMP-UP). The three modalities differ in the combination of reading components (phonological decoding, spelling, fluency, comprehension) that are taught and their organization. Latent change scores were used to examine changes in phonological decoding, fluency, and comprehension for each modality at the group level. In addition, individual students were classified as gainers versus non-gainers (a reading level increase of a year or more vs. less than one year) so that characteristics of gainers and differential sensitivity to instructional modality could be investigated. Findings from both group and individual analyses indicated that reading outcomes were related to modalities of reading instruction. Furthermore, differences in reading gains were seen between students who began treatment with higher reading scores than those with lower reading scores; dependent on modality of treatment. Results, examining group and individual analyses similarities and differences, and the effect the different modalities have on reading outcomes for older struggling readers will be discussed. PMID:25657503

Salvage therapy for locally recurrent prostate cancer after radiation.

PubMed

Marcus, David M; Canter, Daniel J; Jani, Ashesh B; Dobbs, Ryan W; Schuster, David M; Carthon, Bradley C; Rossi, Peter J

2012-12-01

External beam radiotherapy (EBRT) is widely utilized as primary therapy for clinically localized prostate cancer. For patients who develop locally recurrent disease after EBRT, local salvage therapy may be indicated. The primary modalities for local salvage treatment in this setting include radical prostatectomy, cryotherapy, and brachytherapy. To date, there is little data describing outcomes and toxicity associated with each of these salvage modalities. A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. We focused on prospective trials and multi-institutional retrospective series in order to identify the highest level of evidence describing these therapies. The majority of reports describing the use of local salvage treatment for recurrent prostate cancer after EBRT are single-institution, retrospective reports, although small prospective studies are available for salvage cryotherapy and salvage brachytherapy. Clinical outcomes and toxicity for each modality vary widely across studies, which is likely due to the heterogeneity of patient populations, treatment techniques, and definitions of failure. In general, most studies demonstrate that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. As there are no randomized trials comparing salvage treatment modalities for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis, with careful consideration of each patient's disease characteristics and tolerance for the risks of treatment. Additional data, ideally from prospective randomized trials, is needed to guide decision making for patients with local recurrence after EBRT failure.

Social Networking Sites: An Adjunctive Treatment Modality for Psychological Problems

PubMed Central

Menon, Indu S.; Sharma, Manoj Kumar; Chandra, Prabha S.; Thennarasu, K.

2014-01-01

Background: Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Materials and Methods: Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Results: Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. Conclusions: It has implications for developing social networking based adjunctive treatment modality for psychological problems. PMID:25035548

The inducers of immunogenic cell death for tumor immunotherapy.

PubMed

Li, Xiuying

2018-01-01

Immunotherapy is a promising treatment modality that acts by selectively harnessing the host immune defenses against cancer. An effective immune response is often needed to eliminate tumors following treatment which can trigger the immunogenicity of dying tumor cells. Some treatment modalities (such as photodynamic therapy, high hydrostatic pressure or radiotherapy) and agents (some chemotherapeutic agents, oncolytic viruses) have been used to endow tumor cells with immunogenicity and/or increase their immunogenicity. These treatments and agents can boost the antitumor capacity by inducing immune responses against tumor neoantigens. Immunogenic cell death is a manner of cell death that can induce the emission of immunogenic damage-associated molecular patterns (DAMPs). DAMPs are sufficient for immunocompetent hosts to trigger the immune system. This review focuses on the latest developments in the treatment modalities and agents that can induce and/or enhance the immunogenicity of cancer cells.

Social networking sites: an adjunctive treatment modality for psychological problems.

PubMed

Menon, Indu S; Sharma, Manoj Kumar; Chandra, Prabha S; Thennarasu, K

2014-07-01

Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. It has implications for developing social networking based adjunctive treatment modality for psychological problems.

Computational selection of antibody-drug conjugate targets for breast cancer

PubMed Central

Fauteux, François; Hill, Jennifer J.; Jaramillo, Maria L.; Pan, Youlian; Phan, Sieu; Famili, Fazel; O'Connor-McCourt, Maureen

2016-01-01

The selection of therapeutic targets is a critical aspect of antibody-drug conjugate research and development. In this study, we applied computational methods to select candidate targets overexpressed in three major breast cancer subtypes as compared with a range of vital organs and tissues. Microarray data corresponding to over 8,000 tissue samples were collected from the public domain. Breast cancer samples were classified into molecular subtypes using an iterative ensemble approach combining six classification algorithms and three feature selection techniques, including a novel kernel density-based method. This feature selection method was used in conjunction with differential expression and subcellular localization information to assemble a primary list of targets. A total of 50 cell membrane targets were identified, including one target for which an antibody-drug conjugate is in clinical use, and six targets for which antibody-drug conjugates are in clinical trials for the treatment of breast cancer and other solid tumors. In addition, 50 extracellular proteins were identified as potential targets for non-internalizing strategies and alternative modalities. Candidate targets linked with the epithelial-to-mesenchymal transition were identified by analyzing differential gene expression in epithelial and mesenchymal tumor-derived cell lines. Overall, these results show that mining human gene expression data has the power to select and prioritize breast cancer antibody-drug conjugate targets, and the potential to lead to new and more effective cancer therapeutics. PMID:26700623

Development of a 3D ultrasound-guided system for thermal ablation of liver tumors

NASA Astrophysics Data System (ADS)

Neshat, Hamid R. S.; Cool, Derek W.; Barker, Kevin; Gardi, Lori; Kakani, Nirmal; Fenster, Aaron

2013-03-01

Two-dimensional ultrasound (2D US) imaging is commonly used for diagnostic and intraoperative guidance of interventional abdominal procedures including percutaneous thermal ablation of focal liver tumors with radiofrequency (RF) or microwave (MW) induced energy. However, in many situations 2D US may not provide enough anatomical detail and guidance information. Therefore, intra-procedural CT or MR imaging are used in many centers for guidance purposes. These modalities are costly and are mainly utilized to confirm tool placement rather than guiding the insertion. Three-dimensional ultrasound (3D US) has been introduced to address these issues. In this paper, we present our integrated solution to provide 3D US images using a newly developed mechanical transducer with a large field-ofview and without the need for external tracking devices to combine diagnostic and planning information of different modalities for intraoperative guidance. The system provides tools to segment the target(s), plan the treatment, and detect the ablation applicators during the procedure for guiding purposes. We present experimental results used to ensure that our system generates accurate measurements and our early clinical evaluation results. The results suggest that 3D US used for focal liver ablation can provide a more reliable planning and guidance tool compared to 2D US only, and in many cases offers comparable measurements to other alternatives at significantly lower cost, faster time and with no harmful radiation.

Mental Health Disorder Therapeutic Modalities Modified for the GMS.

PubMed

Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

2017-12-01

Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. The finding of this review confirms the therapeutic modalities can provide useful guidance for the prevention and treatment of mental health disorders and the care of the people in the Greater Mekong Sub-region. In addition, the effective interventions should be tested regarding their suitability for the socio-cultural context in the Greater Mekong Subregion.

Mental Health Disorder Therapeutic Modalities Modified for the GMS

PubMed Central

Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

2017-01-01

Background: Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Methods: The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Results: Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. Conclusion: The finding of this review confirms the therapeutic modalities can provide useful guidance for the prevention and treatment of mental health disorders and the care of the people in the Greater Mekong Sub-region. In addition, the effective interventions should be tested regarding their suitability for the socio-cultural context in the Greater Mekong Subregion. PMID:29657562

Non-pharmacological treatment options for refractory epilepsy: an overview of human treatment modalities and their potential utility in dogs.

PubMed

Martlé, Valentine; Van Ham, Luc; Raedt, Robrecht; Vonck, Kristl; Boon, Paul; Bhatti, Sofie

2014-03-01

Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Orthotic management of the neuropathic foot: an interdisciplinary care perspective.

PubMed

Robinson, Christopher; Major, Matthew J; Kuffel, Charles; Hines, Kevin; Cole, Pamela

2015-02-01

Clinical management of the patient with neuropathic foot is becoming commonplace in orthotic clinics worldwide. The presentations that can result from neuropathic foot are diverse, requiring clinicians to understand the pathomechanics of ulceration, infection, and Charcot joint arthropathy to provide effective interventions. The purpose of this clinical perspective is to provide a review of the literature regarding clinical concepts associated with orthotic management of neuropathic foot. Literature review and clinical case study. Relevant literature were reviewed and summarized, and a clinical case study synthesizing reviewed concepts was presented. Given the multifactorial nature of the neuropathic foot, treatments must be multifaceted and patient-specific to effectively address the underlying disease processes. While systemic issues such as peripheral arterial disease are treated by physicians, local issues such as foot deformity are managed by orthotists. Orthotic interventions commonly include custom footwear to reduce the risk of ulceration through creation of a protective environment or targeted plantar offloading. Patient and caregiver education to encourage management compliance is equally as important to ensure successful treatment. Patients with neuropathic foot benefit from an interdisciplinary care approach which engages physicians, wound care practitioners, and orthotists to treat and manage systemic and local problems. Addressing this pathology through interdisciplinary care may positively affect the patient's health status while lowering associated healthcare costs through improved treatment efficacy. The commonality of neuropathic foot and associated complications including ulceration, infection, and Charcot joint arthropathy requires that the patient care team have a fundamental understanding of these pathologies and common treatment modalities. We review orthotic treatment modalities to assist clinicians with the management of patients with neuropathic foot. © The International Society for Prosthetics and Orthotics 2014.

Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects.

PubMed

Savic, Lynn Jeanette; Chapiro, Julius; Geschwind, Jean-François H

2017-02-01

Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed.

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

PubMed Central

Eitan, Renana; Lerer, Bernard

2006-01-01

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

Four novel prosthodontic methods for managing upper airway resistance syndrome: an investigative analysis revealing the efficacy of the new nasopharyngeal aperture guard appliance.

PubMed

Venkat, R; Gopichander, N; Vasantakumar, M

2010-01-01

Obstructive sleep apnea is the most frequent cause for insomnia in the populace. Snoring is mulled over as the potential factor that can lead the sequel to obstructive sleep apnea. Although the etiology and deterrence measures for snoring are yet to be undoubtedly clarified by our scientific sorority, various means of surgical corrections have been affirmed and put into practice, with a substantial degree of success. Despite this, it is implicit that a noninvasive method of managing obstructive sleep apnea is more relevant for overcoming this condition. This manuscript intends to establish how snoring can be controlled prosthodontically by different modalities of scientifically defensible approaches. The most effective among the modalities was affirmed as the investigative analyses of the treatment outcomes with each modality. NOVEL METHODS: Four new methods of managing obstructive sleep apnea--uvula lift appliance, uvula and velopharynx lift appliance, nasopharyngeal aperture guard, and soft palate lift appliance were demonstrated through this article. The four new modalities stated and one conventional modality of mandibular advancement appliance for managing obstructive sleep apnea, a total of five types of appliance therapies, were described with case reports for each. Five individuals undergoing the appliance therapy were chosen for each modality. The treatment outcome with each modality was examined by analysis of clinical predictors and also by means of standard investigation, with nasal and oral endoscopic analyses. Among the five types of appliance therapies, the nasopharyngeal aperture guard provided the best treatment outcome in terms of clinical predictors and endoscopic analyses. Nasopharyngeal aperture guard, the novel method stated in this article is the better modality for managing obstructive sleep apnea, among the five different appliance therapies.

Design optimisation of a TOF-based collimated camera prototype for online hadrontherapy monitoring

NASA Astrophysics Data System (ADS)

Pinto, M.; Dauvergne, D.; Freud, N.; Krimmer, J.; Letang, J. M.; Ray, C.; Roellinghoff, F.; Testa, E.

2014-12-01

Hadrontherapy is an innovative radiation therapy modality for which one of the main key advantages is the target conformality allowed by the physical properties of ion species. However, in order to maximise the exploitation of its potentialities, online monitoring is required in order to assert the treatment quality, namely monitoring devices relying on the detection of secondary radiations. Herein is presented a method based on Monte Carlo simulations to optimise a multi-slit collimated camera employing time-of-flight selection of prompt-gamma rays to be used in a clinical scenario. In addition, an analytical tool is developed based on the Monte Carlo data to predict the expected precision for a given geometrical configuration. Such a method follows the clinical workflow requirements to simultaneously have a solution that is relatively accurate and fast. Two different camera designs are proposed, considering different endpoints based on the trade-off between camera detection efficiency and spatial resolution to be used in a proton therapy treatment with active dose delivery and assuming a homogeneous target.

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Hong, Jin Ki; Jang, Ja Yun; An, Jieun; Lee, Kyu-Sung; Kang, Tong Mook; Shin, Hyun Joon; Suh, Jun-Kyo Francis

2017-01-01

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

PET/PDT theranostics: synthesis and biological evaluation of a peptide-targeted gallium porphyrin.

PubMed

Bryden, Francesca; Savoie, Huguette; Rosca, Elena V; Boyle, Ross W

2015-03-21

The development of novel theranostic agents is an important step in the pathway towards personalised medicine, with the combination of diagnostic and therapeutic modalities into a single treatment agent naturally lending itself to the optimisation and personalisation of treatment. In pursuit of the goal of a molecular theranostic suitable for use as a PET radiotracer and a photosensitiser for PDT, a novel radiolabelled peptide-porphyrin conjugate targeting the α6β1-integrin has been developed. (69/71)Ga and (68)Ga labelling of an azide-functionalised porphyrin has been carried out in excellent yields, with subsequent bioconjugation to an alkyne-functionalised peptide demonstrated. α6β1-integrin expression of two cell lines has been evaluated by flow cytometry, and therapeutic potential of the conjugate demonstrated. Evaluation of the phototoxicity of the porphyrin-peptide theranostic conjugate in comparison to an untargeted control porphyrin in vitro, demonstrated significantly enhanced activity for a cell line with higher α6β1-integrin expression when compared with a cell line exhibiting lower α6β1-integrin expression.

Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low-grade non-Hodgkin's lymphoma.

PubMed

Gordon, Leo I; Witzig, Thomas E; Wiseman, Greg A; Flinn, Ian W; Spies, Stewart S; Silverman, Daniel H; Emmanuolides, Christos; Cripe, Larry; Saleh, Mansoor; Czuczman, Myron S; Olejnik, Teresa; White, Christine A; Grillo-López, Antonio J

2002-02-01

The treatment of malignant lymphoma has improved over the past 20 years, but the majority of patients are not cured. New modalities using targeted therapy based on new information in molecular biology and immunology hold promise for better outcomes with less toxicity. We review data on the use of radiolabeled monoclonal antibodies directed against the CD20 antigen on malignant B cells. We discuss the major radionuclides available, iodine 131 ( 131 I), tositumomab, and yttrium 90 ( 90 Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA) and present data on new approaches in labeling antibodies that have facilitated their use. Clinical trial data with the yttrium-labeled antibodies are discussed. The use of dosimetry as a means for predicting toxicity is discussed, and the questions of long-term toxicity (late effects) are addressed. These targeted approaches to the treatment of malignancy, and lymphoma in particular, hold great promise. Semin Oncol 29 (suppl 2):87-92. Copyright © 2002 by W.B. Saunders Company. Copyright © 2002 W.B. Saunders Company. All rights reserved.

Prediction in a visual language: real-time sentence processing in American Sign Language across development.

PubMed

Lieberman, Amy M; Borovsky, Arielle; Mayberry, Rachel I

2018-01-01

Prediction during sign language comprehension may enable signers to integrate linguistic and non-linguistic information within the visual modality. In two eyetracking experiments, we investigated American Sign language (ASL) semantic prediction in deaf adults and children (aged 4-8 years). Participants viewed ASL sentences in a visual world paradigm in which the sentence-initial verb was either neutral or constrained relative to the sentence-final target noun. Adults and children made anticipatory looks to the target picture before the onset of the target noun in the constrained condition only, showing evidence for semantic prediction. Crucially, signers alternated gaze between the stimulus sign and the target picture only when the sentential object could be predicted from the verb. Signers therefore engage in prediction by optimizing visual attention between divided linguistic and referential signals. These patterns suggest that prediction is a modality-independent process, and theoretical implications are discussed.

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

Extranodal natural killer/T-cell lymphoma: advances in the management.

PubMed

Jaccard, Arnaud; Hermine, Olivier

2011-09-01

Extranodal natural killer (NK)/T-cell lymphoma, nasal-type is a highly aggressive disease more frequent in Asia than in Western countries. There is no consensus treatment. The outcome depends on disease stage. Localized NK/T-cell lymphomas often respond to radiotherapy. In contrast, patients who have extensive disease or who relapse after radiotherapy have a very poor prognosis. Overall, long-term survival in these lymphomas tends to be inferior to that for other aggressive lymphomas. This review focuses on the new management modalities in light of advances in risk stratification, patient monitoring and treatment strategies. Many parameters have been reported to correlate with prognosis and new staging systems have been elaborated. Detecting Epstein-Barr virus (EBV) in the bone marrow is important for staging and measuring EBV DNA in the serum improved monitoring response to therapy. Radiation modalities have been precised and new strategies combining radiation and chemotherapy have been proposed for patients with localized disease. The particular efficacy of L-asparaginase in this disease has been confirmed and L-asparaginase-based regimens have been studied in prospective trials for patients with refractory, relapsing or disseminated disease with good results. Laboratory studies may point the way toward new therapeutic approaches. Early-stage disease is treated by involved-field radiotherapy with adjuvant chemotherapy. L-Asparaginase-containing regimens are the mainstay of treatment for advanced or disseminated disease. The role of targeted therapies, autologous and allogeneic haematopoietic stem cell transplantation is yet to be clearly defined.

Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

PubMed Central

Kang, Tae Wook; Rhim, Hyunchul

2015-01-01

Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

Estrogen Enhances Malignant Phenotypes in Human Salivary Adenoid Cystic Carcinoma Cells.

PubMed

Sumida, Tomoki; Ishikawa, Akiko; Kamata, Y U; Nakano, Hiroyuki; Yamada, Tomohiro; Mori, Yoshihide

2016-06-01

Adenoid cystic carcinoma (SGC) is a common type of salivary gland cancer (SGC). Surgery is the first treatment choice because chemoradiotherapy is usually not effective. Therefore, new treatment modalities are urgently needed. In this study, it was investigated whether the estrogen axis could be a treatment target or not. Adenoid cystic carcinoma (ACC) ACCM cells, were used. The specific cell line lacks estrogen receptor (ER). ER was introduced in ACCM cells, and the effect of 17β-estradiol (E2) was investigated on cell proliferation, cell-cycle distribution, and cell motility. E2 induced cell proliferation, and the S-phase fraction increased in a dose-dependent manner. Cell motility was also up-regulated compared to control cells. The estrogen/ER system up-regulated malignant phenotypes in ER-positive ACC, and hormone therapy may have a potential as effective treatment for this malignancy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Nanoparticle-based drug delivery to the vagina: a review

PubMed Central

Ensign, Laura M.; Cone, Richard; Hanes, Justin

2014-01-01

Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

Recommendations for Management of Patients with Carotid Stenosis

PubMed Central

Lovrencic-Huzjan, Arijana; Rundek, Tatjana; Katsnelson, Michael

2012-01-01

Stroke is a one of the leading causes of morbidity and mortality in the world. Carotid atherosclerosis is recognized as an important factor in stroke pathophysiology and represents a key target in stroke prevention; multiple treatment modalities have been developed to battle this disease. Multiple randomized trials have shown the efficacy of carotid endarterectomy in secondary stroke prevention. Carotid stenting, a newer treatment option, presents a less invasive alternative to the surgical intervention on carotid arteries. Advances in medical therapy have also enabled further risk reduction in the overall incidence of stroke. Despite numerous trials and decades of clinical research, the optimal management of symptomatic and asymptomatic carotid disease remains controversial. We will attempt to highlight some of the pivotal trials already completed, discuss the current controversies and complexities in the treatment decision-making, and postulate on what likely lies ahead. This paper will highlight the complexities of decision-making optimal treatment recommendations for patients with symptomatic and asymptomatic carotid stenosis. PMID:22645702

Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

NASA Astrophysics Data System (ADS)

Sukhikh, E.; Sheino, I.; Vertinsky, A.

2017-09-01

Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer.

PubMed

Xing, Lingxi; Shi, Qiusheng; Zheng, Kailiang; Shen, Ming; Ma, Jing; Li, Fan; Liu, Yang; Lin, Lizhou; Tu, Wenzhi; Duan, Yourong; Du, Lianfang

2016-01-01

Pancreatic cancer, one of the most lethal human malignancies with dismal prognosis, is refractory to existing radio-chemotherapeutic treatment modalities. There is a critical unmet need to develop effective approaches, especially for targeted pancreatic cancer drug delivery. Targeted and drug-loaded nanoparticles (NPs) combined with ultrasound-mediated microbubble destruction (UMMD) have been shown to significantly increase the cellular uptake in vitro and drug retention in vivo, suggesting a promising strategy for cancer therapy. In this study, we synthesized pancreatic cancer-targeting organic NPs that were modified with anti CA19-9 antibody and encapsulated paclitaxol (PTX). The three-block copolymer methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) constituted the skeleton of the NPs. We speculated that the PTX-NPs-anti CA19-9 would circulate long-term in vivo, "actively target" pancreatic cancer cells, and sustainably release the loaded PTX while UMMD would "passively target" the irradiated tumor and effectively increase the permeability of cell membrane and capillary gaps. Our results demonstrated that the combination of PTX-NPs-anti CA19-9 with UMMD achieved a low IC50, significant cell cycle arrest, and cell apoptosis in vitro. In mouse pancreatic tumor xenografts, the combined application of PTX-NP-anti CA19-9 NPs with UMMD attained the highest tumor inhibition rate, promoted the pharmacokinetic profile by increasing AUC, t1/2, and mean residence time (MRT), and decreased clearance. Consequently, the survival of the tumor-bearing nude mice was prolonged without obvious toxicity. The dynamic change in cellular uptake, targeted real-time imaging, and the concentration of PTX in the plasma and tumor were all closely associated with the treatment efficacy both in vitro and in vivo. Our study suggests that PTX-NP-anti CA19-9 NPs combined with UMMD is a promising strategy for the treatment of pancreatic cancer.

A nanocomposite of Au-AgI core/shell dimer as a dual-modality contrast agent for x-ray computed tomography and photoacoustic imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orza, Anamaria; Wu, Hui; Li, Yuancheng

Purpose: To develop a core/shell nanodimer of gold (core) and silver iodine (shell) as a dual-modal contrast-enhancing agent for biomarker targeted x-ray computed tomography (CT) and photoacoustic imaging (PAI) applications. Methods: The gold and silver iodine core/shell nanodimer (Au/AgICSD) was prepared by fusing together components of gold, silver, and iodine. The physicochemical properties of Au/AgICSD were then characterized using different optical and imaging techniques (e.g., HR- transmission electron microscope, scanning transmission electron microscope, x-ray photoelectron spectroscopy, energy-dispersive x-ray spectroscopy, Z-potential, and UV-vis). The CT and PAI contrast-enhancing effects were tested and then compared with a clinically used CT contrast agentmore » and Au nanoparticles. To confer biocompatibility and the capability for efficient biomarker targeting, the surface of the Au/AgICSD nanodimer was modified with the amphiphilic diblock polymer and then functionalized with transferrin for targeting transferrin receptor that is overexpressed in various cancer cells. Cytotoxicity of the prepared Au/AgICSD nanodimer was also tested with both normal and cancer cell lines. Results: The characterizations of prepared Au/AgI core/shell nanostructure confirmed the formation of Au/AgICSD nanodimers. Au/AgICSD nanodimer is stable in physiological conditions for in vivo applications. Au/AgICSD nanodimer exhibited higher contrast enhancement in both CT and PAI for dual-modality imaging. Moreover, transferrin functionalized Au/AgICSD nanodimer showed specific binding to the tumor cells that have a high level of expression of the transferrin receptor. Conclusions: The developed Au/AgICSD nanodimer can be used as a potential biomarker targeted dual-modal contrast agent for both or combined CT and PAI molecular imaging.« less

Active vibration control of thin-plate structures with partial SCLD treatment

NASA Astrophysics Data System (ADS)

Lu, Jun; Wang, Pan; Zhan, Zhenfei

2017-02-01

To effectively suppress the low-frequency vibration of a thin-plate, the strategy adopted is to develop a model-based approach to the investigation on the active vibration control of a clamped-clamped plate with partial SCLD treatment. Firstly, a finite element model is developed based on the constitutive equations of elastic, piezoelectric and viscoelastic materials. The characteristics of viscoelastic materials varying with temperature and frequency are described by GHM damping model. A low-dimensional real modal control model which can be used as the basis for active vibration control is then obtained from the combined reduction. The emphasis is placed on the feedback control system to attenuate the vibration of plates with SCLD treatments. A modal controller in conjunction with modal state estimator is designed to solve the problem of full state feedback, making it much more feasible to real-time control. Finally, the theoretical model is verified by modal test, and an active vibration control is validated by hardware-in-the-loop experiment under different external excitations. The numerical and experimental study demonstrate how the piezoelectric actuators actively control the lower modes (first bending and torsional modes) using modal controller, while the higher frequency vibration attenuated by viscoelastic passive damping layer.

Bitter Melon Reduces Head and Neck Squamous Cell Carcinoma Growth by Targeting c-Met Signaling

PubMed Central

Nerurkar, Pratibha; Gonzalez, Juan G.; Crawford, Susan; Varvares, Mark; Ray, Ratna B.

2013-01-01

Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC. PMID:24147107

Novel mouth-exercising device for oral submucous fibrosis.

PubMed

Patil, Pravinkumar G; Patil, Smita P

2012-10-01

Oral submucous fibrosis (OSMF) is a chronic inflammatory disease resulting in progressive juxtaepithelial fibrosis of the oral soft tissues and can cause increasing difficulty in mastication, swallowing, speaking, and mouth opening. The treatment of severe trismus requires a combination of surgical release and physiotherapy. Often physiotherapy alone can modify tissue remodeling in OSMF to increase oral opening. This article describes the fabrication and use of a new mouth-exercising device that helps the patient to squeeze/stretch the cheek mucosa to increase elasticity. The device can be used as a sole treatment modality or can be used in association with pharmacological and surgical treatment modalities for OSMF. Improvement in mouth opening was observed in four OSMF patients treated with a mouth-exercising device for 6 months as a sole treatment modality. © 2012 by the American College of Prosthodontists.

Revision of orthovoltage chest wall treatment using Monte Carlo simulations.

PubMed

Zeinali-Rafsanjani, B; Faghihi, R; Mosleh-Shirazi, M A; Mosalaei, A; Hadad, K

2017-01-01

Given the high local control rates observed in breast cancer patients undergoing chest wall irradiation by kilovoltage x-rays, we aimed to revisit this treatment modality by accurate calculation of dose distributions using Monte Carlo simulation. The machine components were simulated using the MCNPX code. This model was used to assess the dose distribution of chest wall kilovoltage treatment in different chest wall thicknesses and larger contour or fat patients in standard and mid sternum treatment plans. Assessments were performed at 50 and 100 cm focus surface distance (FSD) and different irradiation angles. In order to evaluate different plans, indices like homogeneity index, conformity index, the average dose of heart, lung, left anterior descending artery (LAD) and percentage target coverage (PTC) were used. Finally, the results were compared with the indices provided by electron therapy which is a more routine treatment of chest wall. These indices in a medium chest wall thickness in standard treatment plan at 50 cm FSD and 15 degrees tube angle was as follows: homogeneity index 2.57, conformity index 7.31, average target dose 27.43 Gy, average dose of heart, lung and LAD, 1.03, 2.08 and 1.60 Gy respectively and PTC 11.19%. Assessments revealed that dose homogeneity in planning target volume (PTV) and conformity between the high dose region and PTV was poor. To improve the treatment indices, the reference point was transferred from the chest wall skin surface to the center of PTV. The indices changed as follows: conformity index 7.31, average target dose 60.19 Gy, the average dose of heart, lung and LAD, 3.57, 6.38 and 5.05 Gy respectively and PTC 55.24%. Coverage index of electron therapy was 89% while it was 22.74% in the old orthovoltage method and also the average dose of the target was about 50 Gy but in the given method it was almost 30 Gy. The results of the treatment study show that the optimized standard and mid sternum treatment for different chest wall thicknesses is with 50 cm FSD and zero (vertical) tube angle, while in large contour patients, it is with 100 cm FSD and zero tube angle. Finally, chest wall kilovoltage and electron therapies were compared, which revealed that electron therapy produces a better dose distribution than kilovoltage therapy.

Spatial working memory for locations specified by vision and audition: testing the amodality hypothesis.

PubMed

Loomis, Jack M; Klatzky, Roberta L; McHugh, Brendan; Giudice, Nicholas A

2012-08-01

Spatial working memory can maintain representations from vision, hearing, and touch, representations referred to here as spatial images. The present experiment addressed whether spatial images from vision and hearing that are simultaneously present within working memory retain modality-specific tags or are amodal. Observers were presented with short sequences of targets varying in angular direction, with the targets in a given sequence being all auditory, all visual, or a sequential mixture of the two. On two thirds of the trials, one of the locations was repeated, and observers had to respond as quickly as possible when detecting this repetition. Ancillary detection and localization tasks confirmed that the visual and auditory targets were perceptually comparable. Response latencies in the working memory task showed small but reliable costs in performance on trials involving a sequential mixture of auditory and visual targets, as compared with trials of pure vision or pure audition. These deficits were statistically reliable only for trials on which the modalities of the matching location switched from the penultimate to the final target in the sequence, indicating a switching cost. The switching cost for the pair in immediate succession means that the spatial images representing the target locations retain features of the visual or auditory representations from which they were derived. However, there was no reliable evidence of a performance cost for mixed modalities in the matching pair when the second of the two did not immediately follow the first, suggesting that more enduring spatial images in working memory may be amodal.

Vogt-Koyanagi-Harada disease.

PubMed

Burkholder, Bryn M

2015-11-01

The purpose of this article is to review the current literature on Vogt-Koyanagi-Harada (VKH) disease, including current treatment options and new research directions. Recent publications on VKH disease show an increased focus on the immunogenetics and immune pathways associated with the development of VKH disease. There have also been advances in imaging modalities and techniques that may help to better elucidate the disease process in eyes with VKH disease. VKH disease is an autoimmune, multisystem inflammatory disorder, the cause of which is still incompletely understood. Continued research may elucidate the causes and triggers of immune dysregulation in this disease, and in doing so, identify novel therapeutic targets.

Current and emerging therapeutic modalities for hyperhidrosis, part 1: conservative and noninvasive treatments.

PubMed

Ram, Ramin; Lowe, Nicholas J; Yamauchi, Paul S

2007-03-01

Approximately 1% to 3% of the US population has hyperhidrosis (HH). HH can be an incapacitating medical condition because it not only hinders patient quality of life but also causes the secondary effect of excess cutaneous sweat. There is a broad spectrum of treatment modalities including topical and systemic therapies, iontophoresis, localized neuroinhibitory injections, and surgical interventions. This article reviews HH and the conservative treatments for the condition.

Modulating the tumor microenvironment with RNA interference as a cancer treatment strategy.

PubMed

Zins, Karin; Sioud, Mouldy; Aharinejad, Seyedhossein; Lucas, Trevor; Abraham, Dietmar

2015-01-01

The tumor microenvironment is composed of accessory cells and immune cells in addition to extracellular matrix (ECM) components. The stromal compartment interacts with cancer cells in a complex crosstalk to support tumor development. Growth factors and cytokines produced by stromal cells support the growth of tumor cells and promote interaction with the vasculature to enhance tumor progression and invasion. The activation of autocrine and paracrine oncogenic signaling pathways by growth factors, cytokines, and proteases derived from both tumor cells and the stromal compartment is thought to play a major role in assisting tumor cells during metastasis. Consequently, targeting tumor-stroma interactions by RNA interference (RNAi)-based approaches is a promising strategy in the search for novel treatment modalities in human cancer. Recent advances in packaging technology including the use of polymers, peptides, liposomes, and nanoparticles to deliver small interfering RNAs (siRNAs) into target cells may overcome limitations associated with potential RNAi-based therapeutics. Newly developed nonviral gene delivery approaches have shown improved anticancer efficacy suggesting that RNAi-based therapeutics provide novel opportunities to elicit significant gene silencing and induce regression of tumor growth. This chapter summarizes our current understanding of the tumor microenvironment and highlights some potential targets for therapeutic intervention with RNAi-based cancer therapeutics.

Non-viral nucleic acid containing nanoparticles as cancer therapeutics.

PubMed

Kozielski, Kristen L; Rui, Yuan; Green, Jordan J

2016-10-01

The delivery of nucleic acids such as DNA and short interfering RNA (siRNA) is promising for the treatment of many diseases, including cancer, by enabling novel biological mechanisms of action. Non-viral nanoparticles are a promising class of nucleic acid carriers that can be designed to be safer and more versatile than traditional viral vectors. In this review, recent advances in the intracellular delivery of DNA and siRNA are described with a focus on non-viral nanoparticle-based delivery methods. Material properties that have enabled successful delivery are discussed as well as applications that have directly been applied to cancer therapy. Strategies to co-deliver different nucleic acids are highlighted, as are novel targets for nucleic acid co-delivery. The treatment of complex genetically-based diseases such as cancer can be enabled by safe and effective intracellular delivery of multiple nucleic acids. Non-viral nanoparticles can be fabricated to deliver multiple nucleic acids to the same cell simultaneously to prevent tumor cells from easily compensating for the knockdown or overexpression of one genetic target. The continued innovation of new therapeutic modalities and non-viral nanotechnologies to provide target-specific and personalized forms of gene therapy hold promise for genetic medicine to treat diseases like cancer in the clinic.

Non-viral nucleic acid containing nanoparticles as cancer therapeutics

PubMed Central

Kozielski, Kristen L.; Rui, Yuan

2016-01-01

Introduction The delivery of nucleic acids such as DNA and short interfering RNA (siRNA) is promising for the treatment of many diseases, including cancer, by enabling novel biological mechanisms of action. Non-viral nanoparticles are a promising class of nucleic acid carriers that can be designed to be safer and more versatile than traditional viral vectors. Areas covered In this review, recent advances in the intracellular delivery of DNA and siRNA are described with a focus on non-viral nanoparticle-based delivery methods. Material properties that have enabled successful delivery are discussed as well as applications that have directly been applied to cancer therapy. Strategies to co-deliver different nucleic acids are highlighted, as are novel targets for nucleic acid co-delivery. Expert opinion The treatment of complex genetically-based diseases such as cancer can be enabled by safe and effective intracellular delivery of multiple nucleic acids. Non-viral nanoparticles can be fabricated to deliver multiple nucleic acids to the same cell simultaneously to prevent tumor cells from easily compensating for the knockdown or overexpression of one genetic target. The continued innovation of new therapeutic modalities and non-viral nanotechnologies to provide target-specific and personalized forms of gene therapy hold promise for genetic medicine to treat diseases like cancer in the clinic. PMID:27248202

Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells.

PubMed

Taratula, Olena; Dani, Raj Kumar; Schumann, Canan; Xu, Hong; Wang, Andrew; Song, Han; Dhagat, Pallavi; Taratula, Oleh

2013-12-15

A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40°C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach. Copyright © 2013 Elsevier B.V. All rights reserved.

miR-139-5p Modulates Radiotherapy Resistance in Breast Cancer by Repressing Multiple Gene Networks of DNA Repair and ROS Defense.

PubMed

Pajic, Marina; Froio, Danielle; Daly, Sheridan; Doculara, Louise; Millar, Ewan; Graham, Peter H; Drury, Alison; Steinmann, Angela; de Bock, Charles E; Boulghourjian, Alice; Zaratzian, Anaiis; Carroll, Susan; Toohey, Joanne; O'Toole, Sandra A; Harris, Adrian L; Buffa, Francesca M; Gee, Harriet E; Hollway, Georgina E; Molloy, Timothy J

2018-01-15

Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo , resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic. Significance: The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. Cancer Res; 78(2); 501-15. ©2017 AACR . ©2017 American Association for Cancer Research.

Methodologies for Verification and Validation of Space Launch System (SLS) Structural Dynamic Models

NASA Technical Reports Server (NTRS)

Coppolino, Robert N.

2018-01-01

Responses to challenges associated with verification and validation (V&V) of Space Launch System (SLS) structural dynamics models are presented in this paper. Four methodologies addressing specific requirements for V&V are discussed. (1) Residual Mode Augmentation (RMA), which has gained acceptance by various principals in the NASA community, defines efficient and accurate FEM modal sensitivity models that are useful in test-analysis correlation and reconciliation and parametric uncertainty studies. (2) Modified Guyan Reduction (MGR) and Harmonic Reduction (HR, introduced in 1976), developed to remedy difficulties encountered with the widely used Classical Guyan Reduction (CGR) method, are presented. MGR and HR are particularly relevant for estimation of "body dominant" target modes of shell-type SLS assemblies that have numerous "body", "breathing" and local component constituents. Realities associated with configuration features and "imperfections" cause "body" and "breathing" mode characteristics to mix resulting in a lack of clarity in the understanding and correlation of FEM- and test-derived modal data. (3) Mode Consolidation (MC) is a newly introduced procedure designed to effectively "de-feature" FEM and experimental modes of detailed structural shell assemblies for unambiguous estimation of "body" dominant target modes. Finally, (4) Experimental Mode Verification (EMV) is a procedure that addresses ambiguities associated with experimental modal analysis of complex structural systems. Specifically, EMV directly separates well-defined modal data from spurious and poorly excited modal data employing newly introduced graphical and coherence metrics.

Evaluation of the U.S. Army Alcohol and Drug Abuse Prevention and Control Program. Phase 2

DTIC Science & Technology

1994-06-13

24 Alcohol Last Use and Frequency of Use by Track ................ 26 ! Cannabis and Cocaine Last Use By Track...Outcome ...................................... 69 Alcohol Track II Probability Results ........................... 70 Cannabis Track I1 Probability...81 Time By Treatment Modality for Alcohol By Track ................. 82 Time By Treatment Modality for Cannabis and Cocaine ............. 84

Experiential Education, Outdoor Adventure As a Modality in Residential Treatment. A Survey of Programs, Principles, Research and Practice.

ERIC Educational Resources Information Center

Duindam, Ton

Orthopedagogisch Centrum (OC) Michiel is a multifunctional regional institution in the Netherlands that serves troubled families and youth at risk. Outdoor programs are used as a treatment modality for adolescents with behavior disorders, drug addictions, or criminal records. Outward Bound was the first experiential outdoor program in the…

Renal Cell Carcinoma: Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review.

PubMed

Prins, Fieke M; Kerkmeijer, Linda G W; Pronk, Anne A; Vonken, Evert-Jan P A; Meijer, Richard P; Bex, Axel; Barendrecht, Maurits M

2017-10-01

The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery, alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance, radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future.

Determining the best treatment for simple bone cyst: a decision analysis.

PubMed

Lee, Seung Yeol; Chung, Chin Youb; Lee, Kyoung Min; Sung, Ki Hyuk; Won, Sung Hun; Choi, In Ho; Cho, Tae-Joon; Yoo, Won Joon; Yeo, Ji Hyun; Park, Moon Seok

2014-03-01

The treatment of simple bone cysts (SBC) in children varies significantly among physicians. This study examined which procedure is better for the treatment of SBC, using a decision analysis based on current published evidence. A decision tree focused on five treatment modalities of SBC (observation, steroid injection, autologous bone marrow injection, decompression, and curettage with bone graft) were created. Each treatment modality was further branched, according to the presence and severity of complications. The probabilities of all cases were obtained by literature review. A roll back tool was utilized to determine the most preferred treatment modality. One-way sensitivity analysis was performed to determine the threshold value of the treatment modalities. Two-way sensitivity analysis was utilized to examine the joint impact of changes in probabilities of two parameters. The decision model favored autologous bone marrow injection. The expected value of autologous bone marrow injection was 0.9445, while those of observation, steroid injection, decompression, and curettage and bone graft were 0.9318, 0.9400, 0.9395, and 0.9342, respectively. One-way sensitivity analysis showed that autologous bone marrow injection was better than that of decompression for the expected value when the rate of pathologic fracture, or positive symptoms of SBC after autologous bone marrow injection, was lower than 20.4%. In our study, autologous bone marrow injection was found to be the best choice of treatment of SBC. However, the results were sensitive to the rate of pathologic fracture after treatment of SBC. Physicians should consider the possibility of pathologic fracture when they determine a treatment method for SBC.

Surgery of primary tumour has survival benefit in metastatic breast cancer with single-organ metastasis, especially bone.

PubMed

Rhu, Jinsoo; Lee, Se Kyung; Kil, Won Ho; Lee, Jeong Eon; Nam, Seok Jin

2015-04-01

Surgery for the primary breast tumour is usually not recommended in metastatic breast cancer (MBC); however, some reports have suggested a benefit of locoregional treatment. We designed this study to evaluate the efficacy of locoregional surgery in MBC. Data for patients diagnosed with MBC at Samsung Medical Center between 1995 and 2011 were retrospectively collected. We compared the survival benefit of all treatment modalities using Cox regression analysis. Subgroup analyses based on number of metastases were performed to delineate the indication for each treatment. Among 262 patients, 40 (15.3%) underwent surgery. Other treatments included chemotherapy (n = 213, 81.3%), radiotherapy (n = 138, 52.7%), hormone therapy (n = 118, 45.0%) and HER2/neu receptor (HER2)-targeted therapy (n = 37, 14.1%). Cox regression analysis showed that surgery (hazard ratios (HR) = 0.51, P < 0.01), hormone therapy (HR = 0.31, P < 0.01) and HER2-targeted therapy (HR = 0.33, P < 0.01) were associated with improved survival, whereas presence of three or more metastatic organs (HR = 1.62, P = 0.03) was associated with poor survival. In patients with metastasis to a single organ, surgery (HR = 0.43, P < 0.01), chemotherapy (HR = 0.62, P = 0.05), hormone therapy (HR = 0.39, P < 0.01) and HER2-targeted therapy (HR = 0.39, P = 0.02) had a survival benefit. Furthermore, for patients with bone-only metastasis, surgery (HR = 0.37, P = 0.02), chemotherapy (HR = 0.42, P < 0.01), hormone therapy (HR = 0.22, P < 0.01) and HER2-targeted therapy (HR = 0.09, P = 0.02) showed a survival benefit. However, only hormone therapy and HER2-targeted therapy had a survival benefit in MBC with metastasis to multiple organs. Surgical control of the primary breast tumour should be considered as a locoregional therapy in combination with systemic therapy in MBC with metastasis to a single organ, especially bone-only metastasis.

Complementary and alternative medicine use by psychiatric inpatients.

PubMed

Elkins, Gary; Rajab, M Hasan; Marcus, Joel

2005-02-01

82 psychiatric inpatients hospitalized for acute care were interviewed about their use of complementary and alternative medicine (CAM) modalities. The clinical diagnoses of respondents included Depressive Disorder (61%), Substance Abuse (26%), Schizophrenia (9%), and Anxiety Disorders (5%). Analysis indicated that 63% used at least one CAM modality within the previous 12 mo. The most frequently used modality was herbal therapies (44%), followed by mind-body therapies such as relaxation or mental imagery, hypnosis, meditation, biofeedback (30%), and spiritual healing by another (30%). Physical modalities such as massage, chiropractic treatment, acupuncture, and yoga were used by 21% of respondents. CAM therapies were used for a variety of reasons ranging from treatment of anxiety and depression to weight loss. However, most respondents indicated they did not discuss such use with their psychiatrist or psychotherapist.

Grammatical Deviations in the Spoken and Written Language of Hebrew-Speaking Children With Hearing Impairments.

PubMed

Tur-Kaspa, Hana; Dromi, Esther

2001-04-01

The present study reports a detailed analysis of written and spoken language samples of Hebrew-speaking children aged 11-13 years who are deaf. It focuses on the description of various grammatical deviations in the two modalities. Participants were 13 students with hearing impairments (HI) attending special classrooms integrated into two elementary schools in Tel Aviv, Israel, and 9 students with normal hearing (NH) in regular classes in these same schools. Spoken and written language samples were collected from all participants using the same five preplanned elicitation probes. Students with HI were found to display significantly more grammatical deviations than their NH peers in both their spoken and written language samples. Most importantly, between-modality differences were noted. The participants with HI exhibited significantly more grammatical deviations in their written language samples than in their spoken samples. However, the distribution of grammatical deviations across categories was similar in the two modalities. The most common grammatical deviations in order of their frequency were failure to supply obligatory morphological markers, failure to mark grammatical agreement, and the omission of a major syntactic constituent in a sentence. Word order violations were rarely recorded in the Hebrew samples. Performance differences in the two modalities encourage clinicians and teachers to facilitate target linguistic forms in diverse communication contexts. Furthermore, the identification of linguistic targets for intervention must be based on the unique grammatical structure of the target language.

Construction of specific magnetic resonance imaging/optical dual-modality molecular probe used for imaging angiogenesis of gastric cancer.

PubMed

Yan, Xuejie; Song, Xiaoyan; Wang, Zhenbo

2017-05-01

The purpose of the study was to construct specific magnetic resonance imaging (MRI)/optical dual-modality molecular probe. Tumor-bearing animal models were established. MRI/optical dual-modality molecular probe was construed by coupling polyethylene glycol (PEG)-modified nano-Fe 3 O 4 with specific targeted cyclopeptide GX1 and near-infrared fluorescent dyes Cy5.5. MRI/optical imaging effects of the probe were observed and the feasibility of in vivo double-modality imaging was discussed. It was found that, the double-modality probe was of high stability; tumor signal of the experimental group tended to be weak after injection of the probe, but rose to a level which was close to the previous level after 18 h (p > 0.05). We successively completed the construction of an ideal MRI/optical dual-modality molecular probe. MRI/optical dual-modality molecular probe which can selectively gather in gastric cancer is expected to be a novel probe used for diagnosing gastric cancer in the early stage.

A fuzzy feature fusion method for auto-segmentation of gliomas with multi-modality diffusion and perfusion magnetic resonance images in radiotherapy.

PubMed

Guo, Lu; Wang, Ping; Sun, Ranran; Yang, Chengwen; Zhang, Ning; Guo, Yu; Feng, Yuanming

2018-02-19

The diffusion and perfusion magnetic resonance (MR) images can provide functional information about tumour and enable more sensitive detection of the tumour extent. We aimed to develop a fuzzy feature fusion method for auto-segmentation of gliomas in radiotherapy planning using multi-parametric functional MR images including apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV). For each functional modality, one histogram-based fuzzy model was created to transform image volume into a fuzzy feature space. Based on the fuzzy fusion result of the three fuzzy feature spaces, regions with high possibility belonging to tumour were generated automatically. The auto-segmentations of tumour in structural MR images were added in final auto-segmented gross tumour volume (GTV). For evaluation, one radiation oncologist delineated GTVs for nine patients with all modalities. Comparisons between manually delineated and auto-segmented GTVs showed that, the mean volume difference was 8.69% (±5.62%); the mean Dice's similarity coefficient (DSC) was 0.88 (±0.02); the mean sensitivity and specificity of auto-segmentation was 0.87 (±0.04) and 0.98 (±0.01) respectively. High accuracy and efficiency can be achieved with the new method, which shows potential of utilizing functional multi-parametric MR images for target definition in precision radiation treatment planning for patients with gliomas.

Hand Movement Deviations in a Visual Search Task with Cross Modal Cuing

ERIC Educational Resources Information Center

Aslan, Asli; Aslan, Hurol

2007-01-01

The purpose of this study is to demonstrate the cross-modal effects of an auditory organization on a visual search task and to investigate the influence of the level of detail in instructions describing or hinting at the associations between auditory stimuli and the possible locations of a visual target. In addition to measuring the participants'…

Radiotherapy and "new" drugs-new side effects?

PubMed Central

2011-01-01

Background and purpose Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments. Materials and methods Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Results Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. Conclusions The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity. PMID:22188921

Dual peptide-mediated targeted delivery of bioactive siRNAs to oral cancer cells in vivo.

PubMed

Alexander-Bryant, Angela A; Zhang, Haiwen; Attaway, Christopher C; Pugh, William; Eggart, Laurence; Sansevere, Robert M; Andino, Lourdes M; Dinh, Lu; Cantini, Liliana P; Jakymiw, Andrew

2017-09-01

Despite significant advances in cancer treatment, the prognosis for oral cancer remains poor in comparison to other cancer types, including breast, skin, and prostate. As a result, more effective therapeutic modalities are needed for the treatment of oral cancer. Consequently, in the present study, we examined the feasibility of using a dual peptide carrier approach, combining an epidermal growth factor receptor (EGFR)-targeting peptide with an endosome-disruptive peptide, to mediate targeted delivery of small interfering RNAs (siRNAs) into EGFR-overexpressing oral cancer cells and induce silencing of the targeted oncogene, cancerous inhibitor of protein phosphatase 2A (CIP2A). Fluorescence microscopy, real-time PCR, Western blot analysis, and in vivo bioimaging of mice containing orthotopic xenograft tumors were used to examine the ability of the dual peptide carrier to mediate specific delivery of bioactive siRNAs into EGFR-overexpressing oral cancer cells/tissues. Co-complexation of the EGFR-targeting peptide, GE11R9, with the endosome-disruptive 599 peptide facilitated the specific uptake of siRNAs into oral cancer cells overexpressing EGFR in vitro with optimal gene silencing observed at a 60:30:1 (GE11R9:599:siRNA) molar ratio. Furthermore, when administered systemically to mice bearing xenograft oral tumors, this dual peptide complex mediated increased targeted delivery of siRNAs into tumor tissues in comparison to the 599 peptide alone and significantly enhanced CIP2A silencing. Herein we provide the first report demonstrating the clinical potential of a dual peptide strategy for siRNA-based therapeutics by synergistically mediating the effective targeting and delivery of bioactive siRNAs into EGFR-overexpressing oral cancer cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimizing the treatment of metastatic castration-resistant prostate cancer: a Latin America perspective.

PubMed

Sade, Juan Pablo; Báez, Carlos Alberto Vargas; Greco, Martin; Martínez, Carlos Humberto; Avitia, Miguel Ángel Álvarez; Palazzo, Carlos; Toriz, Narciso Hernández; Trujillo, Patricia Isabel Bernal; Bastos, Diogo Assed; Schutz, Fabio Augusto; Bella, Santiago; Nogueira, Lucas; Shore, Neal D

2018-03-19

Prostate cancer is a significant burden and cause of mortality in Latin America. This article reviews the treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) and provides consensus recommendations to assist Latin American prostate cancer specialists with clinical decision making. A multidisciplinary expert panel from Latin America reviewed the available data and their individual experience to develop clinical consensus opinions for the use of life-prolonging agents in mCRPC, with consideration given to factors influencing patient selection and treatment monitoring. There is a lack of level 1 evidence for the best treatment sequence or combinations in mCRPC. In this context, consensus recommendations were provided for the use of taxane-based chemotherapies, androgen receptor axis-targeted agents and targeted alpha therapy, for patients in Latin America. Prostate-specific antigen (PSA) changes alone, during treatment, should be treated with caution; PSA may not be a suitable biomarker for radium-223. Bone scans and computed tomography are the standard imaging modalities in Latin America. Imaging should be prompted during treatment where symptomatic decline and/or significant worsening of laboratory evaluations are reported, or where a course of therapy has been completed and another antineoplastic agent is under consideration. Recommendations and guidance for treatment options in Latin America are provided in the context of country-level variable access to approved agents and technologies for treatment monitoring. Patients should be treated with the purpose of prolonging overall survival and preserving quality of life through increasing the opportunity to administer all available life-prolonging therapies when appropriate.

Primary treatments for clinically localized prostate cancer: a comprehensive lifetime cost-utility analysis

PubMed Central

Cooperberg, Matthew R.; Ramakrishna, Naren R.; Duff, Steven B.; Hughes, Kathleen E.; Sadownik, Sara; Smith, Joseph A.; Tewari, Ashutosh K.

2012-01-01

Objectives To characterize the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (dose-escalated 3-dimensional conformal radiation, intensity-modulated radiation, brachytherapy, or combination), using a comprehensive, lifetime decision analytic model. Patients and Methods A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes following primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. Patients could experience remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the U.S. payer perspective, with incorporation of patient costs in a sensitivity analysis. Results Differences in quality-adjusted life years across modalities were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6 to 10.5 for intermediate-risk patients, and 7.8 to 9.3 for high-risk patients. There were no statistically significant differences among surgical modalities, which tended to be more effective than radiation modalities, with the exception of combination external beam + brachytherapy for high-risk disease. Radiation modalities were consistently more expensive than surgical modalities; costs ranged from $19,901 (robot-assisted prostatectomy for low-risk disease) to $50,276 (combination radiation for high-risk disease). These findings were robust to an extensive set of sensitivity analyses. Conclusions Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives. These findings may inform future policy discussions regarding strategies to improve efficiency of treatment selection for localized prostate cancer. PMID:23279038

Biomimetic one-pot synthesis of gold nanoclusters/nanoparticles for targeted tumor cellular dual-modality imaging

NASA Astrophysics Data System (ADS)

Lin, Jing; Zhou, Zhijun; Li, Zhiming; Zhang, Chunlei; Wang, Xiansong; Wang, Kan; Gao, Guo; Huang, Peng; Cui, Daxiang

2013-04-01

Biomimetic synthesis has become a promising green pathway to prepare nanomaterials. In this study, bovine serum albumin (BSA)-conjugated gold nanoclusters/nanoparticles were successfully synthesized in water at room temperature by a protein-directed, solution-phase, green synthetic method. The synthesized BSA-Au nanocomplexes have fluorescence emission (588 nm) of gold nanoclusters and surface plasmon resonance of gold nanoparticles. The BSA-Au nanocomplexes display non-cytotoxicity and excellent biocompatibility on MGC803 gastric cancer cells. After conjugation of folic acid molecules, the obtained BSA-Au nanocomplexes showed highly selective targeting for MGC803 cells and dual-modality dark-field and fluorescence imaging.

Instrumentation of Molecular Imaging on Site-Specific Targeting Fluorescent Peptide for Early Detection of Breast Cancer

NASA Astrophysics Data System (ADS)

Yu, Ping; Ma, Lixin

2012-02-01

In this work we developed two biomedical imaging techniques for early detection of breast cancer. Both image modalities provide molecular imaging capability to probe site-specific targeting dyes. The first technique, heterodyne CCD fluorescence mediated tomography, is a non-invasive biomedical imaging that uses fluorescent photons from the targeted dye on the tumor cells inside human breast tissue. The technique detects a large volume of tissue (20 cm) with a moderate resolution (1 mm) and provides the high sensitivity. The second technique, dual-band spectral-domain optical coherence tomography, is a high-resolution tissue imaging modality. It uses a low coherence interferometer to detect coherent photons hidden in the incoherent background. Due to the coherence detection, a high resolution (20 microns) is possible. We have finished prototype imaging systems for the development of both image modalities and performed imaging experiments on tumor tissues. The spectroscopic/tomographic images show contrasts of dense tumor tissues and tumor necrotic regions. In order to correlate the findings from our results, a diffusion-weighted magnetic resonance imaging (MRI) of the tumors was performed using a small animal 7-Telsa MRI and demonstrated excellent agreement.

Optical imaging of tumor microenvironment

PubMed Central

Wu, Yihan; Zhang, Wenjie; Li, Jinbo; Zhang, Yan

2013-01-01

Tumor microenvironment plays important roles in tumor development and metastasis. Features of the tumor microenvironment that are significantly different from normal tissues include acidity, hypoxia, overexpressed proteases and so on. Therefore, these features can serve as not only biomarkers for tumor diagnosis but also theraputic targets for tumor treatment. Imaging modalities such as optical, positron emission tomography (PET) and magnetic resonance imaging (MRI) have been intensively applied to investigate tumor microenvironment. Various imaging probes targeting pH, hypoxia and proteases in tumor microenvironment were thus well developed. In this review, we will focus on recent examples on fluorescent probes for optical imaging of tumor microenvironment. Construction of these fluorescent probes were based on characteristic feature of pH, hypoxia and proteases in tumor microenvironment. Strategies for development of these fluorescent probes and applications of these probes in optical imaging of tumor cells or tissues will be discussed in this review paper. PMID:23342297

Molecular Mechanisms and Management of a Cutaneous Inflammatory Disorder: Psoriasis

PubMed Central

Cho, Dae Ho; Park, Hyun Jeong

2017-01-01

Psoriasis is a complex chronic inflammatory cutaneous disorder. To date, robust molecular mechanisms of psoriasis have been reported. Among diverse aberrant immunopathogenetic mechanisms, the current model emphasizes the role of Th1 and the IL-23/Th17 axis, skin-resident immune cells and major signal transduction pathways involved in psoriasis. The multiple genetic risk loci for psoriasis have been rapidly revealed with the advent of a novel technology. Moreover, identifying epigenetic modifications could bridge the gap between genetic and environmental risk factors in psoriasis. This review will provide a better understanding of the pathogenesis of psoriasis by unraveling the complicated interplay among immunological abnormalities, genetic risk foci, epigenetic modification and environmental factors of psoriasis. With advances in molecular biology, diverse new targets are under investigation to manage psoriasis. The recent advances in treatment modalities for psoriasis based on targeted molecules are also discussed. PMID:29232931

Effects of photoacoustic imaging and photothermal ablation therapy mediated by targeted hollow gold nanospheres in an orthotopic mouse xenograft model of glioma

PubMed Central

Lu, Wei; Melancon, Marites P.; Xiong, Chiyi; Huang, Qian; Elliott, Andrew; Song, Shaoli; Zhang, Rui; Flores, Leo G.; Gelovani, Juri G.; Wang, Lihong V.; Ku, Geng; Stafford, R. Jason; Li, Chun

2011-01-01

Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography (PAT), a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and angiogenic blood vessels in a mouse model of glioma. Mice were then treated with near-infrared laser, which elevated tumor temperature by 20.7 °C. We found that PTA treatment significantly prolonged the survival of tumor-bearing mice. Taken together, these results demonstrate the feasibility of using a single nanostructure for image-guided local tumor PTA therapy using photoacoustic molecular imaging. PMID:21856744

Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma– associated herpesvirus

PubMed Central

Nun, Tamara K.; Kroll, David J.; Oberlies, Nicholas H.; Soejarto, Djaja D.; Case, Ryan J.; Piskaut, Pius; Matainaho, Teatulohi; Hilscher, Chelsey; Wang, Ling; Dittmer, Dirk P.; Gao, Shou-Jiang; Damania, Blossom

2013-01-01

Tumors associated with Kaposi's sarcoma–associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. Latent viral proteins maintain the viral genome and are required for tumorigenesis. Current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can persist for the lifetime of the host. Thus, targeting latent viral proteins may prove to be an important therapeutic modality for existing tumors as well as in tumor prevention by reducing latent virus load. Here, we describe a novel fluorescence-based screening assay to monitor the maintenance of the Kaposi's sarcoma–associated herpesvirus genome in B lymphocyte cell lines and to identify compounds that induce its loss, resulting in tumor cell death. PMID:17699731

Nanoparticle-induced intraperitoneal hyperthermia and targeted photoablation in treating ovarian cancer

PubMed Central

Wu, Chao-Chih; Yang, Yuh-Cheng; Hsu, Yun-Ting; Wu, T.-C.; Hung, Chien-Fu; Huang, Jung-Tang; Chang, Chih-Long

2015-01-01

Hyperthermic intraperitoneal chemotherapy is effective in treating various intra-abdominal malignancies. However, this therapeutic modality can only be performed during surgical operations and cannot be used repeatedly. We propose repeatedly noninvasive hyperthermia mediated by pegylated silica-core gold nanoshells (pSGNs) in vivo with external near-infrared (NIR) laser irradiation. This study demonstrated that repeated photothermal treatment can effectively eliminate intraperitoneal tumors in mouse ovarian cancer models without damage of normal tissues. By conjugating pSGNs with anti-human CD47 monoclonal antibody, a significant photoablative effect can be achieved using lower amount of pSGNs and shorter NIR laser irradiation. Conjugated pSGNs specifically targeted and bound to cancer cells inside the peritoneal cavity. Our results indicate the possibility of a noninvasive method of repeated hyperthermia and photoablative therapies using nanoparticles. This has substantial clinical potential in treating ovarian and other intraperitoneal cancers. PMID:26318039

N270 sensitivity to conflict strength and working memory: A combined ERP and sLORETA study.

PubMed

Scannella, Sébastien; Pariente, Jérémie; De Boissezon, Xavier; Castel-Lacanal, Evelyne; Chauveau, Nicolas; Causse, Mickaël; Dehais, Frédéric; Pastor, Josette

2016-01-15

The event-related potential N270 component is known to be an electrophysiological marker of the supramodal conflict processing. However little is know about the factors that may modulate its amplitude. In particular, among all studies that have investigated the N270, little or no control of the conflict strength and of the load in working memory have been done leaving a lack in the understanding of this component. We designed a spatial audiovisual conflict task with simultaneous target and cross-modal distractor to evaluate the N270 sensitivity to the conflict strength (i.e., visual target with auditory distractor or auditory target with visual distractor) and the load in working memory (goal task maintenance with frequent change in the target modality). In a first session, participants had to focus on one modality for the target position to be considered (left-hand or right-hand) while the distractor could be at the same side (compatible) or at opposite side (incompatible). In a second session, we used the same set of stimuli as in the first session with an additional distinct auditory signal that clued the participants to frequently switch between the auditory and the visual targets. We found that (1) reaction times and N270 amplitudes for conflicting situations were larger within the auditory target condition compared to the visual one, (2) the increase in target maintenance effort led to equivalent increase of both reaction times and N270 amplitudes within all conditions and (3) the right dorsolateral prefrontal cortex current density was higher for both conflicting and active maintenance of the target situations. These results provide new evidence that the N270 component is an electrophysiological marker of the supramodal conflict processing that is sensitive to the conflict strength and that conflict processing and active maintenance of the task goal are two functions of a common executive attention system. Copyright © 2015 Elsevier B.V. All rights reserved.

Cold Atmospheric Plasma, Created at the Tip of an Elongated Flexible Capillary Using Low Electric Current, Can Slow the Progression of Melanoma

PubMed Central

Binenbaum, Y.; Ben-David, G.; Gil, Z.; Slutsker, Ya. Z.; Ryzhkov, M. A.; Felsteiner, J.; Krasik, Ya. E.; Cohen, J. T.

2017-01-01

Introduction Cold Atmospheric Plasma Jet (CAPJ), with ion temperature close to room temperature, has tremendous potential in biomedical engineering, and can potentially offer a therapeutic option that allows cancer cell elimination without damaging healthy tissue. We developed a hand-held flexible device for the delivery of CAPJ to the treatment site, with a modified high-frequency pulse generator operating at a RMS voltage of <1.2 kV and gas flow in the range 0.3–3 l/min. The aims of our study were to characterize the CAPJ emitted from the device, and to evaluate its efficacy in elimination of cancer cells in-vitro and in-vivo. Methods and Results The power delivered by CAPJ was measured on a floating or grounded copper target. The power did not drastically change over distances of 0–14 mm, and was not dependent on the targets resistance. Temperature of CAPJ-treated target was 23°-36° C, and was dependent on the voltage applied. Spectroscopy indicated that excited OH- radicals were abundant both on dry and wet targets, placed at different distances from the plasma gun. An in-vitro cell proliferation assay demonstrated that CAPJ treatment of 60 seconds resulted in significant reduction in proliferation of all cancer cell lines tested, and that CAPJ activated medium was toxic to cancer cells. In-vivo, we treated cutaneous melanoma tumors in nude mice. Tumor volume was significantly decreased in CAPJ-treated tumors relatively to controls, and high dose per fraction was more effective than low dose per fraction treatment. Importantly, pathologic examination revealed that normal skin was not harmed by CAPJ treatment. Conclusion This preliminary study demonstrates the efficacy of flexible CAPJ delivery system against melanoma progression both in-vitro and in-vivo. It is envisioned that adaptation of CAPJ technology for different kinds of neoplasms use may provide a new modality for the treatment of solid tumors. PMID:28103270

Cold Atmospheric Plasma, Created at the Tip of an Elongated Flexible Capillary Using Low Electric Current, Can Slow the Progression of Melanoma.

PubMed

Binenbaum, Y; Ben-David, G; Gil, Z; Slutsker, Ya Z; Ryzhkov, M A; Felsteiner, J; Krasik, Ya E; Cohen, J T

2017-01-01

Cold Atmospheric Plasma Jet (CAPJ), with ion temperature close to room temperature, has tremendous potential in biomedical engineering, and can potentially offer a therapeutic option that allows cancer cell elimination without damaging healthy tissue. We developed a hand-held flexible device for the delivery of CAPJ to the treatment site, with a modified high-frequency pulse generator operating at a RMS voltage of <1.2 kV and gas flow in the range 0.3-3 l/min. The aims of our study were to characterize the CAPJ emitted from the device, and to evaluate its efficacy in elimination of cancer cells in-vitro and in-vivo. The power delivered by CAPJ was measured on a floating or grounded copper target. The power did not drastically change over distances of 0-14 mm, and was not dependent on the targets resistance. Temperature of CAPJ-treated target was 23°-36° C, and was dependent on the voltage applied. Spectroscopy indicated that excited OH- radicals were abundant both on dry and wet targets, placed at different distances from the plasma gun. An in-vitro cell proliferation assay demonstrated that CAPJ treatment of 60 seconds resulted in significant reduction in proliferation of all cancer cell lines tested, and that CAPJ activated medium was toxic to cancer cells. In-vivo, we treated cutaneous melanoma tumors in nude mice. Tumor volume was significantly decreased in CAPJ-treated tumors relatively to controls, and high dose per fraction was more effective than low dose per fraction treatment. Importantly, pathologic examination revealed that normal skin was not harmed by CAPJ treatment. This preliminary study demonstrates the efficacy of flexible CAPJ delivery system against melanoma progression both in-vitro and in-vivo. It is envisioned that adaptation of CAPJ technology for different kinds of neoplasms use may provide a new modality for the treatment of solid tumors.

TOPICAL REVIEW: The physics, biophysics and technology of photodynamic therapy

NASA Astrophysics Data System (ADS)

Wilson, Brian C.; Patterson, Michael S.

2008-05-01

Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components—light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.

Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors

PubMed Central

Avedian, Raffi S.; Gold, Garry; Ghanouni, Pejman; Pauly, Kim Butts

2015-01-01

This article reviews the fundamental principles and clinical experimental uses of magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) ablation of musculoskeletal tumors. MRgHIFU is a noninvasive treatment modality that takes advantage of the ability of magnetic resonance to measure tissue temperature and uses this technology to guide high-intensity focused ultrasound waves to a specific focus within the human body that results in heat generation and complete thermal necrosis of the targeted tissue. Adjacent normal tissues are spared because of the accurate delivery of thermal energy, as well as, local blood perfusion that provides a cooling effect. MRgHIFU is approved by the Food and Drug Administration for the treatment of uterine fibroids and is used on an experimental basis to treat breast, prostate, liver, bone, and brain tumors. PMID:26120376

Natural Killer Cell Immunotherapy Targeting Cancer Stem Cells

PubMed Central

Luna, Jesus I; Grossenbacher, Steven K.; Murphy, William J; Canter, Robert J

2017-01-01

Introduction Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with “stem-cell” like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. In this report, we review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert Opinion Unlike cytotoxic cancer treatments, NK cells are able to target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells. PMID:27960589

A smart upconversion-based light-triggered polymer for synergetic chemo-photodynamic therapy and dual-modal MR/UCL imaging.

PubMed

Du, Bin; Han, Shuping; Zhao, Feifei; Lim, Kok Hwa; Xi, Hongwei; Su, Xiangjie; Yao, Hanchun; Zhou, Jie

2016-10-01

We have developed a novel nanocomposite to achieve effective therapy and live surveillance of tumor tissue. In this study, fullerene (C 60 ) with iron oxide (Fe 3 O 4 ) nanoparticles and upconversion nanophosphors (UCNPs) was loaded into N-succinyl-N'-4-(2-nitrobenzyloxy)-succinyl-chitosan micelles (SNSC) with good biocompatibility. In addition, hydrophobic anticancer drug docetaxel (DTX) was also loaded into the nanocomposites. The experiments conducted in vitro and in vivo demonstrated that C 60 /Fe 3 O 4 -UCNPs@DTX@SNSC can act synergistically to kill tumor cells by releasing chemotherapy drugs at specific target site as well as generating reactive oxygen using 980nm. In addition, it can also be used for non-invasive deep magnetic resonance and upconversion fluorescence dual-mode imaging. The results indicated that this system provided an efficient method to surmount the drawback of UV or visible light-responsive polymeric systems for controlled drug release and generated reactive oxygen in deep tissues and ultimately realized the integration of dual-modal imaging and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Strategies for early detection of resectable pancreatic cancer

PubMed Central

Okano, Keiichi; Suzuki, Yasuyuki

2014-01-01

Pancreatic cancer is difficult to diagnose at an early stage and generally has a poor prognosis. Surgical resection is the only potentially curative treatment for pancreatic carcinoma. To improve the prognosis of this disease, it is essential to detect tumors at early stages, when they are resectable. The optimal approach to screening for early pancreatic neoplasia has not been established. The International Cancer of the Pancreas Screening Consortium has recently finalized several recommendations regarding the management of patients who are at an increased risk of familial pancreatic cancer. In addition, there have been notable advances in research on serum markers, tissue markers, gene signatures, and genomic targets of pancreatic cancer. To date, however, no biomarkers have been established in the clinical setting. Advancements in imaging modalities touch all aspects of the clinical management of pancreatic diseases, including the early detection of pancreatic masses, their characterization, and evaluations of tumor resectability. This article reviews strategies for screening high-risk groups, biomarkers, and current advances in imaging modalities for the early detection of resectable pancreatic cancer. PMID:25170207

Multi-functional nanoparticles as theranostic agents for the treatment & imaging of pancreatic cancer.

PubMed

Jaidev, L R; Chellappan, David Raj; Bhavsar, Dhiraj Vasanth; Ranganathan, Ravi; Sivanantham, Banudevi; Subramanian, Anuradha; Sharma, Uma; Jagannathan, Narnamangalam R; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

2017-02-01

Theranostics has received considerable attention since both therapy and imaging modalities can be integrated into a single nanocarrier. In this study, fluorescent iron oxide (FIO) nanoparticles and gemcitabine (G) encapsulated poly(lactide-co-glycolide) (PLGA) nanospheres (PGFIO) conjugated with human epidermal growth factor receptor 2, (HER-2) antibody (HER-PGFIO) were prepared and characterized. HER-PGFIO showed the magnetic moment of 10emu/g, relaxivity (r 2 ) of 773mM -1 s -1 and specific absorption rate (SAR) of 183W/g. HER-PGFIO showed a sustained release of gemcitabine for 11days in PBS (pH 7.4). In vitro cytotoxicity evaluation of HER-PGFIO in 3D MIAPaCa-2 cultures showed 50% inhibitory concentration (IC 50 ) of 0.11mg/mL. Subcutaneous tumor xenografts of MIAPaCa-2 in SCID mice were developed and the tumor regression study at the end of 30days showed significant tumor regression (86±3%) in the HER-PGFIO with magnetic hyperthermia (MHT) treatment group compared to control group. In vivo MRI imaging showed the enhanced contrast in HER-PGFIO+MHT treated group compared to control. HER-PGFIO showed significant tumor regression and enhanced MRI in treatment groups, which could be an effective nanocarrier system for the treatment of pancreatic cancer. Combination therapies are best suitable to treat pancreatic cancer. Theranostics are the next generation therapeutics with both imaging and treatment agents encapsulated in a single nanocarrier. The novelty of the present work is the development of targeted nanocarrier that provides chemotherapy, thermotherapy and MRI imaging properties. The present work is the next step in developing the nanocarriers for pancreatic cancer treatment. Different treatment modalities embedding into a single nanocarrier is the biggest challenge that was achieved without compromising the functionality of each other. The surface modification of polymeric nanocarriers for antibody binding and their multifunctional abilities will appeal to wider audience. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.