Manual therapy for plantar heel pain.

PubMed

Pollack, Yosefa; Shashua, Anat; Kalichman, Leonid

2018-03-01

Manual therapy employed in the treatment of plantar heel pain includes joint or soft tissue mobilizations. Efficacy of these methods is still under debate. To determine whether manual therapy, consisting of deep massage, myofascial release or joint mobilization is effective in treating plantar heel pain. A critical review of all available studies with an emphasis on randomized controlled trials (RCTs) was performed. PubMed, PEDro, and Google Scholar databases were searched for keywords relating to plantar heel pain, joint, and soft tissue mobilizations. There were no search limitations or language restrictions. The reference lists of all retrieved articles were searched. The PEDro score was used to assess the quality of the reviewed papers. A total of six relevant RCTs were found: two examined the effectiveness of joint mobilization on plantar heel pain and four the effectiveness of soft tissue techniques. Five studies showed a positive short-term effect after manual therapy treatment, mostly soft tissue mobilizations, with or without stretching exercises for patients with plantar heel pain, compared to other treatments. One study observed that adding joint mobilization to the treatment of plantar heel pain was not effective. The quality of all studies was moderate to high. According to reviewed moderate and high-quality RCTs, soft tissue mobilization is an effective modality for treating plantar heel pain. Outcomes of joint mobilizations are controversial. Further studies are needed to evaluate the short and long-term effect of different soft tissue mobilization techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Manual therapy in osteoarthritis of the hip: outcome in subgroups of patients.

PubMed

Hoeksma, H L; Dekker, J; Ronday, H K; Breedveld, F C; Van den Ende, C H M

2005-04-01

To investigate whether manual therapy has particular benefit in subgroups of patients defined on the basis of hip function, range of joint motion, pain and radiological deterioration. The study was performed in the out-patient clinic of physical therapy of a large hospital. Data on 109 patients with OA of the hip (clinical ACR criteria) participating in a randomized clinical trial on the effects of manual therapy were used. The outcomes for hip function (Harris hip score), range of joint motion (ROM) and pain (VAS) were compared for specific subgroups. Subgroups were assigned by the median split method. The interaction effect between subgroup and treatment was tested using multiple regression analysis. No differences were observed in the effect of manual therapy in specific subgroups of patients defined on the basis of baseline levels of hip function, pain and ROM. On the basis of radiological grading of osteoarthritis (OA), we found that patients with severe radiological grading of OA had significantly worse outcome on ROM as a result of manual therapy than patients with mild or moderate radiological grading of OA. A significant interaction effect was found for only 1 out of 12 hypotheses investigated. Therefore, we conclude that there is no evidence for the particular benefit of manual therapy in subgroups of patients.

Manual Therapy for Hip Osteoarthritis: A Systematic Review and Meta-analysis.

PubMed

Wang, Qiong; Wang, Teng-teng; Qi, Xiao-feng; Yao, Min; Cui, Xue-jun; Wang, Yong-jun; Liang, Qian-qian

2015-11-01

Hip osteoarthritis (HOA) is one of the major causes of disability in seniors and is costly to society. Manual therapy is one therapeutic approach to treating HOA. To assess the effect of manual therapy compared to the placebo or wait-list/no treatment or a minimal intervention control for HOA at post-treatment and short-, intermediate- and long-term follow-ups. A systematic review and meta-analysis of randomized controlled trials (RCTs). Hospital outpatient clinic in China. We searched PubMed, EMBASE, the Cochrane Library, CINAHL, ISI web of knowledge, and Chinese databases from the inception to October 2014 without language restrictions. References of systematic reviews and other related reviews, files in our department, and conference proceedings as grey literature were also screened by hand. RCTs compared manual therapy to the placebo, wait-list/no treatment or a minimal intervention control with an appropriate and precise description of randomization. Two reviewers independently conducted the search results identification, data extraction, and methodological quality assessment. We calculated the risk difference (RD) for dichotomous data and the mean difference (MD) or standardized mean difference (SMD) for continuous data in a fixed or random effect model. The primary outcomes were self-reported pain in the past week and physical function. The secondary outcomes were the quality of life, global perceived effect, patients' satisfaction, cost, and adverse events. Six studies involving 515 HOA patients were included. Five of the 6 studies ranked as high quality in the methodological assessment. Immediately post-treatment, there was low-quality evidence that manual therapy could not statistically significantly relieve pain (SMD: -0.07 [95%CI -0.38 to 0.24]); for physical function, a moderate quality of evidence showed that manual therapy could not improve the physical function significantly (SMD: 0.14 [95%CI -0.08 to 0.37]). We still found low-quality evidence that

Manual therapy in the treatment of patients with hemophilia B and inhibitor.

PubMed

Cuesta-Barriuso, Rubén; Trelles-Martínez, Roberto O

2018-01-22

The main clinical manifestations of hemophilia are muscle and joint bleeding. Recurrent bleeding leads to a degenerative process known as hemophilic arthropathy. The development of inhibitors (antibodies against FVIII/FIX concentrates) is the main complication in the treatment of hemophilia. The objective was to assess the safety and efficacy of manual therapy treatment in a patient with hemophilia and inhibitor. A 26-year-old patient with hemophilia B and inhibitor received physiotherapy treatment based on manual therapy for 3 months, with a frequency of 2 sessions per week. The joint status was evaluated using the Hemophilia Joint Health Score; pain was assessed with the Visual Analog Scale; and the range of movement was evaluated using a universal goniometer. The patient developed no joint bleeding in the knees or ankles as a result of the physiotherapy treatment. Following treatment, improvements were noted in the range of movement of knees and ankles, the perception of pain in both knees, and ankle functionality. Until now, manual therapy using joint traction was contraindicated in patients with hemophilia and inhibitor, as it was feared to cause possible joint bleeding. This is the first case study to address the safety and efficacy of manual therapy in a patient with hemophilia and an inhibitor. The results of this study may help to establish which manual therapy treatments are indicated in patients with hemophilic arthropathy and inhibitors. Thus, a physiotherapy program based on manual therapy may be safe in patients with hemophilia and inhibitor and such therapy may improve joint condition, pain, and joint range of motion in patients with hemophilia and inhibitor. Randomized clinical trials are needed to confirm the results of this case study.

The Use of Treatment Manuals in Cognitive Therapy: Experience and Issues.

ERIC Educational Resources Information Center

Dobson, Keith S.; Shaw, Brian F.

1988-01-01

Traces historical developments in use of treatment manuals in psychotherapy research and reviews characteristics that have facilitated development of cognitive therapy manuals. Reviews arguments in favor of and opposed to further development of treatment manuals. Discusses relevant research and suggests three areas for future treatment manual…

Manual therapy in adults with tension-type headache: A systematic review.

PubMed

Cumplido-Trasmonte, C; Fernández-González, P; Alguacil-Diego, I M; Molina-Rueda, F

2018-03-07

Tension-type headache is the most common primary headache, with a high prevalence and a considerable socioeconomic impact. Manual physical therapy techniques are widely used in the clinical field to treat the symptoms associated with tension-type headache. This systematic review aims to determine the effectiveness of manual and non-invasive therapies in the treatment of patients with tension-type headache. We conducted a systematic review of randomised controlled trials in the following databases: Brain, PubMed, Web of Science, PEDro, Scopus, CINAHL, and Science Direct. Ten randomised controlled trials were included for analysis. According to these studies, manual therapy improves symptoms, increasing patients' well-being and improving the outcome measures analysed. Manual therapy has positive effects on pain intensity, pain frequency, disability, overall impact, quality of life, and craniocervical range of motion in adults with tension-type headache. None of the techniques was found to be superior to the others; combining different techniques seems to be the most effective approach. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

[Manual trigger point therapy of shoulder pain : Randomized controlled study of effectiveness].

PubMed

Sohns, S; Schnieder, K; Licht, G; von Piekartz, H

2016-12-01

Although chronic shoulder pain is highly prevalent and myofascial trigger points (mTrP) are thought to be found in the majority of patients with shoulder complaints, the influence on the pain mechanism remains unclear. There are only very few controlled clinical studies on the effects of manual trigger point compression therapy. This randomized controlled trial (RCT) compared the short-term effects of manual trigger point compression therapy (n = 6) with manual sham therapy (n = 6) in patients with unilateral shoulder pain due to myofascial syndrome (MFS). The measurement data were collected before and after two sessions of therapy. Pressure pain thresholds (PPT) of mTrP and symmetrically located points on the asymptomatic side were measured together with neutral points in order to detect a potential unilateral or generalized hyperalgesia. Additionally, the pain was assessed on a visual analog scale (VAS) at rest and during movement and the neck disability index (NDI) and disabilities of the arm, shoulder and hand (DASH) questionnaires were also completed and evaluated. Both treatment modalities led to a significant improvement; however, the manual trigger point compression therapy was significantly more effective in comparison to sham therapy, as measured by different parameters. The significant improvement of PPT values in the interventional group even at sites that were not directly treated, indicates central mechanisms in pain threshold modulation induced by manual compression therapy. The weaker but still measurable effects of sham therapy might be explained by the sham modality being a hands on technique or by sufficient stimulation of the trigger point region during the diagnostics and PPT measurements.

Exercise, education, manual-therapy and taping compared to education for patellofemoral osteoarthritis: a blinded, randomised clinical trial.

PubMed

Crossley, K M; Vicenzino, B; Lentzos, J; Schache, A G; Pandy, M G; Ozturk, H; Hinman, R S

2015-09-01

Patellofemoral joint osteoarthritis (PFJ OA) contributes considerably to knee OA symptoms. This study aimed to determine the efficacy of a PFJ-targeted exercise, education manual-therapy and taping program compared to OA education alone, in participants with PFJ OA. A randomised, participant-blinded and assessor-blinded clinical trial was conducted in primary-care physiotherapy. 92 people aged ≥40 years with symptomatic and radiographic PFJ OA participated. Physiotherapists delivered the PFJ-targeted exercise, education, manual-therapy and taping program, or the OA-education (control condition) in eight sessions over 12 weeks. Primary outcomes at 3-month (primary) and 9-month follow-up: (1) patient-perceived global rating of change (2) pain visual analogue scale (VAS) (100 mm); and (3) activities of daily living (ADL) subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS). 81 people (88%) completed the 3-month follow-up and data analysed on an intention-to-treat basis. Between-group baseline similarity for participant characteristics was observed. The exercise, education, manual-therapy and taping program resulted in more people reporting much improvement (20/44) than the OA-education group (5/48) (number needed to treat 3 (95% confidence interval (CI) 2 to 5)) and greater pain reduction (mean difference: -15.2 mm, 95% CI -27.0 to -3.4). No significant effects on ADL were observed (5.8; 95% CI -0.6 to 12.1). At 9 months there were no significant effects for self-report of improvement, pain (-10.5 mm, 95% CI -22.7 to 1.8) or ADL (3.0, 95% CI -3.7 to 9.7). Exercise, education, manual-therapy and taping can be recommended to improve short-term patient rating of change and pain severity. However over 9-months, both options were equivalent. Australian New Zealand Clinical Trials Registry (ACTRN12608000288325): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82878. Copyright © 2015 Osteoarthritis Research Society International. Published

Validation of an educative manual for patients with head and neck cancer submitted to radiation therapy 1

PubMed Central

da Cruz, Flávia Oliveira de Almeida Marques; Ferreira, Elaine Barros; Vasques, Christiane Inocêncio; da Mata, Luciana Regina Ferreira; dos Reis, Paula Elaine Diniz

2016-01-01

Abstract Objective: develop the content and face validation of an educative manual for patients with head and neck cancer submitted to radiation therapy. Method: descriptive methodological research. The Theory of Psychometrics was used for the validation process, developed by 15 experts in the theme area of the educative manual and by two language and publicity professionals. A minimum agreement level of 80% was considered to guarantee the validity of the material. Results: the items addressed in the assessment tool of the educative manual were divided in three blocks: objectives, structure and format, and relevance. Only one item, related to the sociocultural level of the target public, obtained an agreement rate <80%, and was reformulated based on the participants' suggestions. All other items were considered appropriate and/or complete appropriate in the three blocks proposed: objectives - 92.38%, structure and form - 89.74%, and relevance - 94.44%. Conclusion: the face and content validation of the educative manual proposed were attended to. This can contribute to the understanding of the therapeutic process the head and neck cancer patient is submitted to during the radiation therapy, besides supporting clinical practice through the nursing consultation. PMID:27305178

Manualization of Occupational Therapy Interventions: Illustrations from the Pressure Ulcer Prevention Research Program

PubMed Central

Blanche, Erna Imperatore; Fogelberg, Donald; Diaz, Jesus; Carlson, Mike; Clark, Florence

2011-01-01

The manualization of a complex occupational therapy intervention is a crucial step in ensuring treatment fidelity for both clinical application and research purposes. Towards this latter end, intervention manuals are essential for assuring trustworthiness and replicability of randomized controlled trials (RCT’s) that aim to provide evidence of the effectiveness of occupational therapy. In this paper, literature on the process of intervention manualization is reviewed. The prescribed steps are then illustrated through our experience in implementing the University of Southern California/Rancho Los Amigos National Rehabilitation Center’s collaborative Pressure Ulcer Prevention Project (PUPP). In this research program, qualitative research provided the initial foundation for manualization of a multifaceted occupational therapy intervention designed to reduce incidence of medically serious pressure ulcers in people with SCI. PMID:22214116

Occupational and Physical Therapy Services, School Based Programs: An Organizational Manual, 1982-83.

ERIC Educational Resources Information Center

McKee, Marlene, Comp.; And Others

A 1982-83 manual on school-based occupational therapy and physical therapy (OT/PT) services in Texas is presented. Contents include: guidelines, evaluation forms, student and therapists' documentation forms, and policy/procedures manuals for a suburban independent school district and a rural independent school district. Part I provides the…

Development of a manualized protocol of massage therapy for clinical trials in osteoarthritis.

PubMed

Ali, Ather; Kahn, Janet; Rosenberger, Lisa; Perlman, Adam I

2012-10-04

Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists' clinical judgment and maintaining consistency with a prior pilot study. The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Clinicaltrials.gov NCT00970008 (18 August 2009).

Exercise therapy, manual therapy, or both, for osteoarthritis of the hip or knee: a factorial randomised controlled trial protocol.

PubMed

Abbott, J Haxby; Robertson, M Clare; McKenzie, Joanne E; Baxter, G David; Theis, Jean-Claude; Campbell, A John

2009-02-08

Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA) of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis) aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether:1. Exercise therapy versus no exercise therapy improves disability at 12 months;2. Manual physiotherapy versus no manual therapy improves disability at 12 months;3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months. This is a 2 x 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a) a supervised multi-modal exercise therapy programme; (b) an individualised manual therapy programme; (c) both exercise therapy and manual therapy; or, (d) no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200). The MOA Trial will be the first to investigate the effectiveness and cost-effectiveness of providing physiotherapy programmes of this kind

Manual therapy compared with physical therapy in patients with non-specific neck pain: a randomized controlled trial.

PubMed

Groeneweg, Ruud; van Assen, Luite; Kropman, Hans; Leopold, Huco; Mulder, Jan; Smits-Engelsman, Bouwien C M; Ostelo, Raymond W J G; Oostendorp, Rob A B; van Tulder, Maurits W

2017-01-01

Manual therapy according to the School of Manual Therapy Utrecht (MTU) is a specific type of passive manual joint mobilization. MTU has not yet been systematically compared to other manual therapies and physical therapy. In this study the effectiveness of MTU is compared to physical therapy, particularly active exercise therapy (PT) in patients with non-specific neck pain. Patients neck pain, aged between 18-70 years, were included in a pragmatic randomized controlled trial with a one-year follow-up. Primary outcome measures were global perceived effect and functioning (Neck Disability Index), the secondary outcome was pain intensity (Numeric Rating Scale for Pain). Outcomes were measured at 3, 7, 13, 26 and 52 weeks. Multilevel analyses (intention-to-treat) were the primary analyses for overall between-group differences. Additional to the primary and secondary outcomes the number of treatment sessions of the MTU group and PT group was analyzed. Data were collected from September 2008 to February 2011. A total of 181 patients were included. Multilevel analyses showed no statistically significant overall differences at one year between the MTU and PT groups on any of the primary and secondary outcomes. The MTU group showed significantly lower treatment sessions compared to the PT group (respectively 3.1 vs. 5.9 after 7 weeks; 6.1 vs. 10.0 after 52 weeks). Patients with neck pain improved in both groups without statistical significantly or clinically relevant differences between the MTU and PT groups during one-year follow-up. ClinicalTrials.gov Identifier: NCT00713843.

A clinical perspective on a pain neuroscience education approach to manual therapy.

PubMed

Louw, Adriaan; Nijs, Jo; Puentedura, Emilio J

2017-07-01

In recent years, there has been an increased interest in pain neuroscience education (PNE) in physical therapy. There is growing evidence for the efficacy of PNE to decrease pain, disability, fear-avoidance, pain catastrophization, limited movement, and health care utilization in people struggling with pain. PNE teaches people in pain more about the biology and physiology of their pain experience including processes such as central sensitization, peripheral sensitization, allodynia, inhibition, facilitation, neuroplasticity and more. PNE's neurobiological model often finds itself at odds with traditional biomedical models used in physical therapy. Traditional biomedical models, focusing on anatomy, pathoanatomy, and biomechanics have been shown to have limited efficacy in helping people understand their pain, especially chronic pain, and may in fact even increase a person's pain experience by increasing fear-avoidance and pain catastrophization. An area of physical therapy where the biomedical model is used a lot is manual therapy. This contrast between PNE and manual therapy has seemingly polarized followers from each approach to see PNE as a 'hands-off' approach even having clinicians categorize patients as either in need of receiving PNE (with no hands-on), or hands-on with no PNE. In this paper, we explore the notion of PNE and manual therapy co-existing. PNE research has shown to have immediate effects of various clinical signs and symptoms associated with central sensitization. Using a model of sensitization (innocuous, noxious, and allodynia), we argue that PNE can be used in a manual therapy model, especially treating someone where the nervous system has become increasingly hypervigilant. Level of Evidence : VII.

Targeted Therapy for Cancer

Cancer.gov

Targeted therapy is a type of cancer treatment that targets the changes in cancer cells that help them grow, divide, and spread. Learn how targeted therapy works against cancer and about side effects that may occur.

Management of Chronic Lateral Epicondylitis With Manual Therapy and Local Cryostimulation: A Pilot Study.

PubMed

Richer, Nadia; Marchand, Andrée-Anne; Descarreaux, Martin

2017-12-01

The purpose of this pilot study was to evaluate the feasibility and efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. The control group (n = 19) was treated with manual therapy consisting of soft-tissue therapy and radial head mobilizations. The experimental group (n = 18) received cryostimulation in addition to manual therapy care similar to that for the control group. Both protocols consisted of 8 treatments over a 4-week period. Outcome measures included pain intensity (visual analog scale), pain-free grip strength (handheld dynamometer), and functional index (Patient-Rated Tennis Elbow Evaluation questionnaire). Assessments were performed at baseline, postintervention, and 3-month follow-up. Adherence and dropout rates were also considered. Both groups exhibited significant improvements in pain intensity and functional index at postintervention assessments, which were maintained at follow-up. All participants attended the prescribed number of treatments, but 27% were lost at follow-up. Minor adverse events were reported after cryostimulation in 4 cases. This study indicated that it is feasible to complete a clinical trial evaluating the efficacy of adding cryostimulation to manual therapy in patients with chronic lateral epicondylitis. On the basis of these preliminary data, the combination of cryostimulation and manual therapy care did not provide any additional benefits in both the short term and the long term. Manual myofascial point treatment and mobilization techniques yielded positive outcomes in chronic lateral epicondylitis. Further studies should focus on the sole therapeutic effect of cryostimulation in both patients with acute and those with chronic conditions.

The ability of a sustained within-session finding of pain reduction during traction to dictate improved outcomes from a manual therapy approach on patients with osteoarthritis of the hip.

PubMed

Wright, Alexis A; Abbott, J Haxby; Baxter, Dave; Cook, Chad

2010-09-01

THE OBJECTIVES OF THIS STUDY WERE TO: (1) determine the association of a within-session finding after traction of the hip with self-report of well-being, pain, and self-report of function at 9 weeks; and (2) to determine if the interactions between the within-session finding and the outcome measure are different between groups of patients with hip OA who receive and who do not receive manual therapy. Data were retrospectively analysed in 70 subjects who were part of a randomized control trial. Correlation analyses of within-session findings from the initial visit after traction of a concordantly painful hip were compared to self-report measures for function, pain, and well-being at 9 weeks. A comparison of slope coefficients between manual therapy and non-manual therapy groups was performed to determine the interactive aspects of the within-session finding. Although the correlations for the manual therapy group were higher than for the supervised neglect group, none of the correlational analyses for both groups was strong or significant. Significant differences in the slope coefficients for well-being and pain were found, suggesting that the interactions between the within-session findings and the targeted outcomes were different in the manual therapy group versus supervised neglect group. These findings suggest that within-session findings during the initial evaluation are not strongly related to a positive outcome after manual therapy, although the interaction of the finding of a within-session change and the use of manual therapy is more compelling than the finding in a sample of patients who did not receive manual therapy.

Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

PubMed

Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

2017-06-01

The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

Considerations to improve the safety of cervical spine manual therapy.

PubMed

Hutting, Nathan; Kerry, Roger; Coppieters, Michel W; Scholten-Peeters, Gwendolijne G M

2018-02-01

Manipulation and mobilisation of the cervical spine are well established interventions in the management of patients with headache and/or neck pain. However, their benefits are accompanied by potential, yet rare risks in terms of serious adverse events, including neurovascular insult to the brain. A recent international framework for risk assessment and management offers directions in the mitigation of this risk by facilitating sound clinical reasoning. The aim of this article is to critically reflect on and summarize the current knowledge about cervical spine manual therapy and to provide guidance for clinical reasoning for cervical spine manual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparing the effects of manual therapy versus electrophysical agents in the management of knee osteoarthritis.

PubMed

Ali, Syed Shahzad; Ahmed, Syed Imran; Khan, Muhammad; Soomro, Rabail Rani

2014-07-01

To evaluate the effectiveness of Manual Therapy in comparison to Electrophysical agents in Knee Osteoarthritis. Total 50 patients with knee osteoarthritis were recruited from OPD of orthopedics civil hospital and Institute Of Physical Medicine & Rehabilitation, Dow University of Health Sciences Karachi. All those patients who fulfilled inclusion criteria were selected on voluntary basis. Selected patients were equally divided and randomly assigned into two groups with age and gender matching. The Manual therapy group received program of Maitland joint mobilization whereas Electrophysical Agent group received a program of TENS and cold pack. Both group received a program of exercise therapy as well. Patients received 3 treatment sessions per week for 4 successive weeks. Clinical assessment was performed using WOMAC index at baseline and on 12th treatment session. Both study groups showed clinically and statistically considerable improvements in WOMAC index. However, Related 2 sample t-test showed better clinical results in Manual Therapy group (p = 0.000) than Electrophysical Agents group (p = 0.008). The mean improvement in total WOMAC index was relatively higher in Manual Therapy group (22.36 ± 13.91) than Electrophysical Agent group (9.72 ± 6.10). This study concluded that manual therapy is clinically more effective in decreasing pain, stiffness and improving physical function in knee osteoarthritis.

Effects of manual therapy and exercise targeting the hips in patients with low-back pain-A randomized controlled trial.

PubMed

Bade, Michael; Cobo-Estevez, Manuel; Neeley, Darren; Pandya, Jeevan; Gunderson, Travis; Cook, Chad

2017-08-01

The benefits of providing manual therapy and exercise targeting the hips in individuals with mechanical low-back pain (LBP) are not well established. The objective in this study is to determine whether a formal prescriptive treatment protocol for the hips improves outcomes in patients with a primary complaint of mechanical LBP. Eighty-four (84) subjects (50 males, 46.1 ± 16.2 years) were randomized to 1 of 2 groups: pragmatic treatment of the lumbar spine only (LBP) (n = 39) or pragmatic treatment of the lumbar spine and prescriptive treatment of bilateral hips (LBP + HIP) (n = 45). Pragmatic treatment of the lumbar spine was based upon published clinical guidelines. Prescriptive treatment of the hips involved the use of 3 hip exercises targeting the gluteal musculature and 3 mobilization techniques targeting the hips. Subjects were assessed at baseline, 2 weeks, and at discharge with the following measures: Modified Oswestry Disability Index, Numeric Pain Rating Scale, a global rating of change (GRoC) score, the patient acceptable symptom state (PASS), and patient satisfaction. At 2 weeks, significant differences between groups differences were found in GRoC and patient satisfaction (P < .05) favoring the LBP + HIP group. At discharge, there were significant differences on the Modified Oswestry Disability Index, numeric pain rating scale, GRoC, and patient satisfaction favoring the LBP + HIP group (P < .05). Effect sizes were small to medium. Our findings suggest that a prescriptive treatment of the hips may be of clinical value to individuals presenting with the primary complaint of mechanical LBP. © 2017 John Wiley & Sons, Ltd.

Manual Therapy in the Treatment of Idiopathic Scoliosis. Analysis of Current Knowledge.

PubMed

Czaprowski, Dariusz

2016-10-28

Apart from the recommended specific physiotherapy, the treatment of idiopathic scoliosis (IS) also incorporates non-specific manual therapy (NMT). The aim of this paper is to assess the efficacy of NMT (manual therapy, chiropractic, osteopathy) used in the treatment of children and adolescents with IS. The study analysed systematic reviews (Analysis 1) and other recent scientific publications (Analysis 2). Analysis 1 encompassed papers on the use of NMT in patients with IS. Works concerning specific physiotherapy (SP) or bracing (B) and other types of scoliosis were excluded from the analysis. Inclusion criteria for Analysis 2 were: treatment with NMT; subjects aged 10-18 years with IS. The following types of papers were excluded: works analysing NMT combined with SP or B, reports concerning adult pa tients, analyses of single cases and publications included in Analysis 1. Analysis 1: six systematic reviews contained 6 papers on the efficacy of NMT in the treatment of IS. The results of these studies are contradictory, ranging from Cobb angle reduction to no treatment effects whatsoever. The papers analysed are characterised by poor methodological quality: small group sizes, incomplete descriptions of the study groups, no follow-up and no control groups. Analysis 2: in total, 217 papers were found. None of them met the criteria set for the analysis. 1. Few papers verifying the efficacy of manual therapy, chiropractic and osteopathy in the treatment of idiopathic scoliosis have been published to date. 2. The majority are experimental studies with poor methodology or observational case studies. 3. At present, the efficacy of non-specific manual therapy in the treatment of patients with idiopathic scoliosis cannot be reliably evaluated. 4. It is necessary to conduct further research based on appropriate methods (prospective, rando mi s ed, controlled studies) in order to reliably assess the usefulness of non-specific manual therapy in the treatment of idiopathic

Manual therapy intervention for a patient with a total hip arthroplasty revision.

PubMed

Howard, Paul D; Levitsky, Beth

2007-12-01

Case report. A 73-year-old active woman with a total hip arthroplasty, who later had revision surgery, developed left hip and buttock pain 2 years after the revision surgery, subsequent to lifting her foot while seated. This movement was performed so that her spouse could assist her in putting on her sock and shoe. During the first physical therapy session, the patient exhibited a forward-flexed trunk posture and difficulty weight bearing on the involved lower limb. The patient was successfully treated with manual therapy techniques and a home exercise program. The manual therapy techniques included long-axis hip distraction, lateral hip distraction, posterior-to-anterior hip joint mobilization, and a contract-relax proprioceptive neuromuscular facilitation technique. The patient's home program consisted of long-axis hip distraction, performed by her spouse, and standing lower limb pendular movements into flexion and extension. Pain scale ratings, posture and gait observations, strength, range of motion, and return to functional activities served as outcome measures. After 1 physical therapy visit, in which manual therapy techniques were utilized, the patient had a significant decrease in hip symptoms. The patient and spouse were compliant with the home exercise program and continued with physical therapy for 3 more visits, and the patient ultimately became symptom free. The patient returned to all previous activities, including household chores, cooking, and a walking program. The patient was contacted at 6 months, 1 year, and 4 years, and reported no recurrences of hip or buttock symptoms. Manual therapy techniques and home exercises described in this case report were apparently effective in eliminating symptoms and returning this patient, who had total hip arthroplasty and revision surgery 2 years earlier, to all previous functional activities after a dressing incident produced hip and buttock symptoms.

Botulinum toxin type A combined with cervical spine manual therapy for masseteric hypertrophy in a patient with Alzheimer-type dementia: a case report.

PubMed

Villafañe, Jorge H; Fernandez-de-Las-Peñas, Cesar; Pillastrini, Paolo

2012-12-01

The purpose of this case study is to present the findings of combining botulinum toxin type A (BoNT-A) and cervical spine manual therapy to address masseter muscle spasticity in a patient with Alzheimer-type dementia. A 78-year-old woman with bilateral spasticity of the masseteric regions for 2 years was referred for physiotherapy. She had trismus and bruxism, and could neither close nor open her mouth normally; thus, she was unable to be fed orally in a normal manner. The patient underwent combined treatment with BoNT-A and cervical spine manual therapy. A medical physician (neurologist) performed the BoNT-A injections into 2 points at the center of the lower third of the masseter muscle. A physical therapist performed manual therapy interventions targeted at the cervical spine. Manual therapy started the day after the BoNT-A injection and continued for 5 sessions per week for a total period of 2 weeks. Clinical outcomes were measured including spasticity (Modified Ashworth Scale), functionality (Barthel Index), and jaw opening. Outcomes were conducted at baseline, 2 weeks after treatment, and at 2-month follow-up session after finishing the treatment. The patient improved in all of the outcomes at the end of treatment, and these results were maintained during the follow-up. After treatment, the patient was able to feed with minimal caregiver dependency because oral feeding was possible. The patient in this study responded positively to a combination of BoNT-A and manual therapy, resulting in decreased masseter muscles spasticity and improved trismus and bruxism.

Targeted Therapy Database (TTD): A Model to Match Patient's Molecular Profile with Current Knowledge on Cancer Biology

PubMed Central

Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M.; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-01-01

Background The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. Objective To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. Methods To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. Results and Conclusions We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit

Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

PubMed

Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-08-10

The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the

IS MANUAL THERAPY A RATIONAL APPROACH TO IMPROVING HEALTH-RELATED QUALITY OF LIFE IN PEOPLE WITH ARTHRITIS?

PubMed Central

Cameron, Melainie

2002-01-01

Background: People with arthritic disease are advised to participate in gentle exercise on a regular basis, and pursue long-term medication regimes. Alternative therapies are also used by people with arthritis, and may sometimes be recommended by rheumatologists and other medical personnel. Alternative therapies may be divided into two types: active therapies, in which the patient takes a driving role, and passive therapies, in which the therapy cannot proceed unless driven by a therapist. Objective: To review the effectiveness of manual therapy in improving the health-related quality of life (HRQOL) of people with two common arthritis conditions: Osteoarthritis and rheumatoid arthritis. Discussion: Massage, and other passive (practitioner-driven) manual therapies, have been anecdotally reported to improve health-related quality of life (HRQOL) in people with arthritis. Many manual therapists consult with patients who have arthritic diseases, receive referrals from rheumatologists, and consider the arthritic diseases to be within their field of practise. Although there is empirical evidence that manual therapy with some types of arthritis is beneficial, the level of effectiveness however is under-researched. Medical authorities are reluctant to endorse manual therapies for arthritis due to a lack of scientific evidence demonstrating efficacy, safety, and cost effectiveness. PMID:17987169

Can Independent Judges Recognize Different Psychotherapies? An Experience with Manual-Guided Therapies.

ERIC Educational Resources Information Center

Luborsky, Lester; And Others

1982-01-01

Tested whether independent judges could recognize three different manual-guided psychotherapies, drug counseling, supportive-expressive psychotherapy, and cognitive-behavioral using a special rating form containing scales for the characteristic aspects of each type. Results indicated that manual-guided therapies can be reliably recognized.…

The role of the vestibular system in manual target localization

NASA Technical Reports Server (NTRS)

Barry, Susan R.; Mueller, S. Alyssa

1995-01-01

Astronauts experience perceptual and sensory-motor disturbances during spaceflight and immediately after return to the 1-g environment of Earth. During spaceflight, sensory information from the eyes, limbs and vestibular organs is reinterpreted by the central nervous system so that astronauts can produce appropriate body movements in microgravity. Alterations in sensory-motor function may affect eye-head-hand coordination and, thus, the crewmember's ability to manually locate objects in extrapersonal space. Previous reports have demonstrated that crewmembers have difficulty in estimating joint and limb position and in pointing to memorized target positions on orbit and immediately postflight. One set of internal cues that may assist in the manual localization of objects is information from the vestibular system. This system contributes to our sense of the body's position in space by providing information on head position and movement and the orientation of the body with respect to gravity. Research on the vestibular system has concentrated on its role in oculo-motor control. Little is known about the role that vestibular information plays in manual motor control, such as reaching and pointing movements. Since central interpretation of vestibular information is altered in microgravity, it is important to determine its role in this process. This summer, we determined the importance of vestibular information in a subject's ability to point accurately toward a target in extrapersonal space. Subjects were passively rotated across the earth-vertical axis and then asked to point back to a previously-seen target. In the first paradigm, the subjects used both visual and vestibular cues for the pointing response, while, in the second paradigm, subjects used only vestibular information. Subjects were able to point with 85 percent accuracy to a target using vestibular information alone. We infer from this result that vestibular input plays a role in the spatial programming of

Why Neck Pain Patients Are Not Referred to Manual Therapy: A Qualitative Study among Dutch Primary Care Stakeholders

PubMed Central

Dikkers, Marije F.; Westerman, Marjan J.; Rubinstein, Sidney M.; van Tulder, Maurits W.; Anema, Johannes R.

2016-01-01

Background Treatment of neck pain with manual therapy demonstrated to be more effective and cost-effective than general practitioner (GP) care or physiotherapy in a high quality RCT in the Netherlands in 2002. However, referral to manual therapy for neck pain is still relatively low. This study aims to explore the barriers and facilitators affecting the implementation of manual therapy in neck pain management in primary care. Methods An explorative study was conducted comprising semi-structured interviews with GPs (n = 13), physiotherapists (n = 10), manual therapists (n = 7) and their patients with neck pain (n = 27), and three focus groups with additional stakeholders (n = 10–12 per group). A thematic analysis approach was used. Results Different barriers and facilitators for referral were found for patients, GPs and physiotherapists on the individual level, but also in the interaction between stakeholders and their context. Individual perceptions such as knowledge and beliefs about manual therapy for neck pain either impeded or facilitated referral. Fear for complications associated with cervical manipulation was an important barrier for patients as well as GPs. For GPs and physiotherapists it was important whether they perceived it was part of their professional role to refer for manual therapy. Existing relations formed referral behavior, and the trust in a particular practitioner was a recurrent theme among GPs and physiotherapist as well as patients. The contextual factor availability of manual therapy played a role for all stakeholders. Conclusions Barriers and facilitators were found especially in individual perceptions on manual therapy for neck pain (e.g. knowledge and beliefs), the interaction between stakeholders (e.g. collaboration and trust) and the organizational context. Implementation strategies that focus on these different aspects seem to be likely to optimize referral rates and the use of manual therapy in primary care management of neck pain

Influence of manual therapy on functional mobility after joint injury in a rat model.

PubMed

Ruhlen, Rachel L; Snider, Eric J; Sargentini, Neil J; Worthington, Bart D; Singh, Vineet K; Pazdernik, Vanessa K; Johnson, Jane C; Degenhardt, Brian F

2013-10-01

Animal models can be used to investigate manual therapy mechanisms, but testing manipulation in animal models is problematic because animals cannot directly report their pain. To develop a rat model of inflammatory joint injury to test the efficacy of manual therapy in reducing nociception and restoring function. The authors induced acute inflammatory joint injury in rats by injecting carrageenan into the ankle and then measured voluntary running wheel activity in treated and untreated rats. Treatments included manual therapy applied to the ankle and knee of the injured limb and several analgesic medications (eg, morphine, ketorolac, prednisone). Intra-articular injection of carrageenan to the ankle produced significant swelling (diameter of the ankle increased by 64% after injection; P=.004) and a robust reduction in voluntary running wheel activity (running distance reduced by 91% compared with controls; P<.001). Injured rats gradually returned to running levels equal to controls over 10 days. Neither manual therapy nor analgesic medications increased running wheel activity relative to untreated rats. Voluntary running wheel activity appears to be an appropriate functional measure to evaluate the impact of an acute inflammatory joint injury. However, efforts to treat the injury did not restore running relative to untreated rats.

Manual therapy as a conservative treatment for adolescent idiopathic scoliosis: a systematic review

PubMed Central

Romano, Michele; Negrini, Stefano

2008-01-01

Background The treatment of adolescent idiopathic scoliosis is contingent upon many variables. Simple observation is enough for less serious curvatures, but for very serious cases surgical intervention could be proposed. Between these there is a wide range of different treatments. Manual therapy is commonly used: the aim of this paper is to verify the data existing in the literature on the efficacy of this approach. Methods A systematic review of the scientific literature published internationally has been performed. We have included in the term manual therapy all the manipulative and generally passive techniques performed by an external operator. In a more specific meaning, osteopathic, chiropractic and massage techniques have been considered as manipulative therapeutic methods. We performed our systematic research in Medline, Embase, Cinhal, Cochrane Library, Pedro with the following terms: idiopathic scoliosis combined with chiropractic; manipulation; mobilization; manual therapy; massage; osteopathy; and therapeutic manipulation. The criteria for inclusion were as follows: Any kind of research; diagnosis of adolescent idiopathic scoliosis; patients treated exclusively by one of the procedures established as a standard for this review (chiropractic manipulation, osteopathic techniques, massage); and outcome in Cobb degrees. Results We founded 145 texts, but only three papers were relevant to our study. However, no one of the three satisfied all the required inclusion criteria because they were characterized by a combination of manual techniques and other therapeutic approaches. Conclusion The lack of any kind of serious scientific data does not allow us to draw any conclusion on the efficacy of manual therapy as an efficacious technique for the treatment of Adolescent idiopathic scoliosis. PMID:18211702

Manual therapy as a conservative treatment for adolescent idiopathic scoliosis: a systematic review.

PubMed

Romano, Michele; Negrini, Stefano

2008-01-22

The treatment of adolescent idiopathic scoliosis is contingent upon many variables. Simple observation is enough for less serious curvatures, but for very serious cases surgical intervention could be proposed. Between these there is a wide range of different treatments. Manual therapy is commonly used: the aim of this paper is to verify the data existing in the literature on the efficacy of this approach. A systematic review of the scientific literature published internationally has been performed. We have included in the term manual therapy all the manipulative and generally passive techniques performed by an external operator. In a more specific meaning, osteopathic, chiropractic and massage techniques have been considered as manipulative therapeutic methods. We performed our systematic research in Medline, Embase, Cinhal, Cochrane Library, Pedro with the following terms: idiopathic scoliosis combined with chiropractic; manipulation; mobilization; manual therapy; massage; osteopathy; and therapeutic manipulation. The criteria for inclusion were as follows: Any kind of research; diagnosis of adolescent idiopathic scoliosis; patients treated exclusively by one of the procedures established as a standard for this review (chiropractic manipulation, osteopathic techniques, massage); and outcome in Cobb degrees. We founded 145 texts, but only three papers were relevant to our study. However, no one of the three satisfied all the required inclusion criteria because they were characterized by a combination of manual techniques and other therapeutic approaches. The lack of any kind of serious scientific data does not allow us to draw any conclusion on the efficacy of manual therapy as an efficacious technique for the treatment of Adolescent idiopathic scoliosis.

Changes in rat spinal cord gene expression after inflammatory hyperalgesia of the joint and manual therapy.

PubMed

Ruhlen, Rachel L; Singh, Vineet K; Pazdernik, Vanessa K; Towns, Lex C; Snider, Eric J; Sargentini, Neil J; Degenhardt, Brian F

2014-10-01

Mobilization of a joint affects local tissue directly but may also have other effects that are mediated through the central nervous system. To identify differential gene expression in the spinal cords of rats with or without inflammatory joint injury after manual therapy or no treatment. Rats were randomly assigned to 1 of 4 treatment groups: no injury and no touch (NI/NT), injury and no touch (I/NT), no injury and manual therapy (NI/MT), and injury and manual therapy (I/MT). We induced acute inflammatory joint injury in the rats by injecting carrageenan into an ankle. Rats in the no-injury groups did not receive carrageenan injection. One day after injury, rats received manual therapy to the knee of the injured limb. Rats in the no-touch groups were anesthetized without receiving manual therapy. Spinal cords were harvested 30 minutes after therapy or no touch, and spinal cord gene expression was analyzed by microarray for 3 comparisons: NI/NT vs I/NT, I/MT vs I/NT, and NI/NT vs NI/MT. Three rats were assigned to each group. Of 38,875 expressed sequence tags, 755 were differentially expressed in the NI/NT vs I/NT comparison. For the other comparisons, no expressed sequence tags were differentially expressed. Cluster analysis revealed that the differentially expressed sequence tags were over-represented in several categories, including ion homeostasis (enrichment score, 2.29), transmembrane (enrichment score, 1.55), and disulfide bond (enrichment score, 2.04). An inflammatory injury to the ankle of rats caused differential expression of genes in the spinal cord. Consistent with other studies, genes involved in ion transport were among those affected. However, manual therapy to the knees of injured limbs or to rats without injury did not alter gene expression in the spinal cord. Thus, evidence for central nervous system mediation of manual therapy was not observed. © 2014 The American Osteopathic Association.

Targeted enzyme prodrug therapies.

PubMed

Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

2010-09-01

The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

Subacromial impingement syndrome--effectiveness of physiotherapy and manual therapy.

PubMed

Gebremariam, Lukas; Hay, Elaine M; van der Sande, Renske; Rinkel, Willem D; Koes, Bart W; Huisstede, Bionka M A

2014-08-01

The subacromial impingement syndrome (SIS) includes the rotator cuff syndrome, tendonitis and bursitis of the shoulder. Treatment includes surgical and non-surgical modalities. Non-surgical treatment is used to reduce pain, to decrease the subacromial inflammation, to heal the compromised rotator cuff and to restore satisfactory function of the shoulder. To select the most appropriate non-surgical intervention and to identify gaps in scientific knowledge, we explored the effectiveness of the interventions used, concentrating on the effectiveness of physiotherapy and manual therapy. The Cochrane Library, PubMed, EMBASE, PEDro and CINAHL were searched for relevant systematic reviews and randomised clinical trials (RCTs). Two reviewers independently extracted data and assessed the methodological quality. A best-evidence synthesis was used to summarise the results. Two reviews and 10 RCTs were included. One RCT studied manual therapy as an add-on therapy to self-training. All other studies studied the effect of physiotherapy: effectiveness of exercise therapy, mobilisation as an add-on therapy to exercises, ultrasound, laser and pulsed electromagnetic field. Moderate evidence was found for the effectiveness of hyperthermia compared to exercise therapy or ultrasound in the short term. Hyperthermia and exercise therapy were more effective in comparison to controls or placebo in the short term (moderate evidence). For the effectiveness of hyperthermia, no midterm or long-term results were studied. In the midterm, exercise therapy gave the best results (moderate evidence) compared to placebo or controls. For other interventions, conflicting, limited or no evidence was found. Some physiotherapeutic treatments seem to be promising (moderate evidence) to treat SIS, but more research is needed before firm conclusions can be drawn. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of adaptation of vestibulo-ocular reflex function on manual target localization

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Merkle, L. A.; Barry, S. R.; Huebner, W. P.; Cohen, H. S.; Mueller, S. A.; Fordice, J.

2000-01-01

The goal of the present study was to determine if adaptive modulation of vestibulo-ocular reflex (VOR) function is associated with commensurate alterations in manual target localization. To measure the effects of adapted VOR on manual responses we developed the Vestibular-Contingent Pointing Test (VCP). In the VCP test, subjects pointed to a remembered target following passive whole body rotation in the dark. In the first experiment, subjects performed VCP before and after wearing 0.5X minifying lenses that adaptively attenuate horizontal VOR gain. Results showed that adaptive reduction in horizontal VOR gain was accompanied by a commensurate change in VCP performance. In the second experiment, bilaterally labyrinthine deficient (LD) subjects were tested to confirm that vestibular cues were central to the spatial coding of both eye and hand movements during VCP. LD subjects performed significantly worse than normal subjects. These results demonstrate that adaptive change in VOR can lead to alterations in manual target localization.

The effectiveness of manual therapy in treating cervicogenic dizziness: a systematic review.

PubMed

Yaseen, Khalid; Hendrick, Paul; Ismail, Ayah; Felemban, Mohannad; Alshehri, Mansour Abdullah

2018-01-01

[Purpose] This review provides an evaluation of the evidence for the effectiveness of using manual therapy to treat cervicogenic dizziness. [Subjects and Methods] The literature was systematically searched on the May 2, 2016 using the following online databases: Medline, EMBASE, CINAHL and PEDro. This review included randomised controlled trials and compared the efficacy of manual therapy for the treatment of cervicogenic dizziness, compared to other types of intervention. This study measured changes based on dizziness intensity and frequency. [Results] The primary search found 30 articles, but only four articles met the inclusion criteria. Assessment of methodological quality was performed by two researchers using the PEDro scale. The level of evidence was determined using a recognised grading scale. Three out of the four articles were deemed to have high methodological quality, while the fourth was rated as moderate quality. The attributed level of evidence was moderate (level 2). [Conclusion] Manual therapy is potentially effective for managing cervicogenic dizziness. However, due to the heterogeneity of the results and techniques and the low number of studies, further research is recommended to provide conclusive evidence.

Effectiveness of Manual Therapy and Stretching for Baseball Players With Shoulder Range of Motion Deficits.

PubMed

Bailey, Lane B; Thigpen, Charles A; Hawkins, Richard J; Beattie, Paul F; Shanley, Ellen

Baseball players displaying deficits in shoulder range of motion (ROM) are at increased risk of arm injury. Currently, there is a lack of consensus regarding the best available treatment options to restore shoulder ROM. Instrumented manual therapy with self-stretching will result in clinically significant deficit reductions when compared with self-stretching alone. Controlled laboratory study. Shoulder ROM and humeral torsion were assessed in 60 active baseball players (mean age, 19 ± 2 years) with ROM deficits (nondominant - dominant, ≥15°). Athletes were randomly assigned to receive a single treatment of instrumented manual therapy plus self-stretching (n = 30) or self-stretching only (n = 30). Deficits in internal rotation, horizontal adduction, and total arc of motion were compared between groups immediately before and after a single treatment session. Treatment effectiveness was determined by mean comparison data, and a number-needed-to-treat (NNT) analysis was used for assessing the presence of ROM risk factors. Prior to intervention, players displayed significant ( P < 0.001) dominant-sided deficits in internal rotation (-26°), total arc of motion (-18°), and horizontal adduction (-17°). After the intervention, both groups displayed significant improvements in ROM, with the instrumented manual therapy plus self-stretching group displaying greater increases in internal rotation (+5°, P = 0.010), total arc of motion (+6°, P = 0.010), and horizontal adduction (+7°, P = 0.004) compared with self-stretching alone. For horizontal adduction deficits, the added use of instrumented manual therapy with self-stretching decreased the NNT to 2.2 (95% CI, 2.1-2.4; P = 0.010). Instrumented manual therapy with self-stretching significantly reduces ROM risk factors in baseball players with motion deficits when compared with stretching alone. The added benefits of manual therapy may help to reduce ROM deficits in clinical scenarios where stretching alone is

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee: a randomized controlled trial. 1: clinical effectiveness.

PubMed

Abbott, J H; Robertson, M C; Chapple, C; Pinto, D; Wright, A A; Leon de la Barra, S; Baxter, G D; Theis, J-C; Campbell, A J

2013-04-01

To evaluate the clinical effectiveness of manual physiotherapy and/or exercise physiotherapy in addition to usual care for patients with osteoarthritis (OA) of the hip or knee. In this 2 × 2 factorial randomized controlled trial, 206 adults (mean age 66 years) who met the American College of Rheumatology criteria for hip or knee OA were randomly allocated to receive manual physiotherapy (n = 54), multi-modal exercise physiotherapy (n = 51), combined exercise and manual physiotherapy (n = 50), or no trial physiotherapy (n = 51). The primary outcome was change in the Western Ontario and McMaster osteoarthritis index (WOMAC) after 1 year. Secondary outcomes included physical performance tests. Outcome assessors were blinded to group allocation. Of 206 participants recruited, 193 (93.2%) were retained at follow-up. Mean (SD) baseline WOMAC score was 100.8 (53.8) on a scale of 0-240. Intention to treat analysis showed adjusted reductions in WOMAC scores at 1 year compared with the usual care group of 28.5 (95% confidence interval (CI) 9.2-47.8) for usual care plus manual therapy, 16.4 (-3.2 to 35.9) for usual care plus exercise therapy, and 14.5 (-5.2 to 34.1) for usual care plus combined exercise therapy and manual therapy. There was an antagonistic interaction between exercise therapy and manual therapy (P = 0.027). Physical performance test outcomes favoured the exercise therapy group. Manual physiotherapy provided benefits over usual care, that were sustained to 1 year. Exercise physiotherapy also provided physical performance benefits over usual care. There was no added benefit from a combination of the two therapies. Australian New Zealand Clinical Trials Registry ACTRN12608000130369. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Manualization of Occupational Therapy Using Ayres Sensory Integration® for Autism.

PubMed

Hunt, Joanne; van Hooydonk, Elke; Faller, Patricia; Mailloux, Zoe; Schaaf, Roseann

2017-07-01

This article reports on the development of a Stage 3 manual (following pilot effectiveness study) for implementing occupational therapy using Ayres Sensory Integration® (OT/ASI) for children with autism spectrum disorders to enhance participation in daily occupations. Three stakeholder groups were surveyed to aid in translation of manual from research to practice (i.e., Stage 3 manual) and an expert consensus meeting was held to finalize recommendations. Data indicated that the manuals usability could be improved by including a section on frequently encountered problems and solutions, and by including video case examples. Also recommended were greater chapter uniformity, improved clarity of forms and charts, and inclusion of a glossary. Changes were made and subject to expert review and consensus using modified Delphi process. The Stage 3 manual has been rigorously vetted and is ready for practice and research replication.

Efficacy of manual therapy in the treatment of tension-type headache. A systematic review from 2000-2013.

PubMed

Lozano López, C; Mesa Jiménez, J; de la Hoz Aizpurúa, J L; Pareja Grande, J; Fernández de Las Peñas, C

2016-01-01

To study the efficacy of manual therapy in the treatment of tension-type headache (TTH) by assessing the quality of randomized control trials (RCTs) published from the year 2000 to April 2013. A search was performed in the following databases: MEDLINE, EBSCO, CINAHL, SCOPUS, PEDRO and OVID. An analysis was made of RCT including patients with TTH receiving any manual therapy, and assessing outcome measures including the intensity, and frequency or duration of the headache. Two independent referees reviewed the methodological quality of RCTs using the Jadad scale. Data from the studies were extracted by two different reviewers. A total of fourteen RCTs were selected. Twelve studies showed acceptable quality (Jadad scale ≥3), and the remaining 2 had low quality (Jadad=2). The studies showed positive results, including reduction in headache intensity and/or frequency, reduction of medication consumption, and improvement in quality of life. The effectiveness of manual therapy for TTH cannot be completely assessed due to the heterogeneity in study design, outcome measures, and different treatments. Nevertheless, the results suggest patients with TTH receiving manual therapies showed better progress than those receiving conventional treatment or placebo. Further studies of high quality using manual therapy protocols, and also including standardized outcome measures, are now needed to clarify the efficacy of manual therapy in the management of TTH. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Effectiveness of exercise therapy and manual mobilisation in ankle sprain and functional instability: a systematic review.

PubMed

van der Wees, Philip J; Lenssen, Anton F; Hendriks, Erik J M; Stomp, Derrick J; Dekker, Joost; de Bie, Rob A

2006-01-01

This study critically reviews the effectiveness of exercise therapy and manual mobilisation in acute ankle sprains and functional instability by conducting a systematic review of randomised controlled trials. Trials were searched electronically and manually from 1966 to March 2005. Randomised controlled trials that evaluated exercise therapy or manual mobilisation of the ankle joint with at least one clinically relevant outcome measure were included. Internal validity of the studies was independently assessed by two reviewers. When applicable, relative risk (RR) or standardised mean differences (SMD) were calculated for individual and pooled data. In total 17 studies were included. In thirteen studies the intervention included exercise therapy and in four studies the effects of manual mobilisation of the ankle joint was evaluated. Average internal validity score of the studies was 3.1 (range 1 to 7) on a 10-point scale. Exercise therapy was effective in reducing the risk of recurrent sprains after acute ankle sprain: RR 0.37 (95% CI 0.18 to 0.74), and with functional instability: RR 0.38 (95% CI 0.23 to 0.62). No effects of exercise therapy were found on postural sway in patients with functional instability: SMD: 0.38 (95% CI -0.15 to 0.91). Four studies demonstrated an initial positive effect of different modes of manual mobilisation on dorsiflexion range of motion. It is likely that exercise therapy, including the use of a wobble board, is effective in the prevention of recurrent ankle sprains. Manual mobilisation has an (initial) effect on dorsiflexion range of motion, but the clinical relevance of these findings for physiotherapy practice may be limited.

Manual therapy directed at the knee or lumbopelvic region does not influence quadriceps spinal reflex excitability.

PubMed

Grindstaff, Terry L; Pietrosimone, Brian G; Sauer, Lindsay D; Kerrigan, D Casey; Patrie, James T; Hertel, Jay; Ingersoll, Christopher D

2014-08-01

Manual therapies, directed to the knee and lumbopelvic region, have demonstrated the ability to improve neuromuscular quadriceps function in individuals with knee pathology. It remains unknown if manual therapies may alter impaired spinal reflex excitability, thus identifying a potential mechanism in which manual therapy may improve neuromuscular function following knee injury. To determine the effect of local and distant mobilisation/manipulation interventions on quadriceps spinal reflex excitability. Seventy-five individuals with a history of knee joint injury and current quadriceps inhibition volunteered for this study. Participants were randomised to one of five intervention groups: lumbopelvic manipulation (grade V), lumbopelvic manipulation positioning (no thrust), grade IV patellar mobilisation, grade I patellar mobilisation, and control (no treatment). Changes in spinal reflex excitability were quantified by assessing the Hoffmann reflex (H-reflex), presynaptic, and postsynaptic excitability. A hierarchical linear-mixed model for repeated measures was performed to compare changes in outcome variables between groups over time (pre, post 0, 30, 60, 90 min). There were no significant differences in H-reflex, presynaptic, or postsynaptic excitability between groups across time. Manual therapies directed to the knee or lumbopelvic region did not acutely change quadriceps spinal reflex excitability. Although manual therapies may improve impairments and functional outcomes the underlying mechanism does not appear to be related to changes in spinal reflex excitability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bioengineering Strategies for Designing Targeted Cancer Therapies

PubMed Central

Wen, Xuejun

2014-01-01

The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

The Effectiveness of Manual Therapy for Relieving Pain, Stiffness, and Dysfunction in Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

PubMed

Xu, Qinguang; Chen, Bei; Wang, Yueyi; Wang, Xuezong; Han, Dapeng; Ding, Daofang; Zheng, Yuxin; Cao, Yuelong; Zhan, Hongsheng; Zhou, Yao

2017-05-01

Knee osteoarthritis (KOA) is the most common form of arthritis, leading to pain disability in seniors and increased health care utilization. Manual therapy is one widely used physical treatment for KOA. To evaluate the effectiveness and adverse events (AEs) of manual therapy compared to other treatments for relieving pain, stiffness, and physical dysfunction in patients with KOA. A systematic review and meta-analysis of manual therapy for KOA. We searched PubMed, EMBASE, the Cochrane Library, and Chinese databases for relevant randomized controlled trials (RCTs) of manual therapy for patients with KOA from the inception to October 2015 without language restrictions. RCTs compared manual therapy to the placebo or other interventional control with an appropriate description of randomization. Two reviewers independently conducted the search results identification, data extraction, and methodological quality assessment. The methodological quality was assessed by PEDro scale. Pooled data was expressed as standard mean difference (SMD), with 95% confident intervals (CIs) in a random effects model. The meta-analysis of manual therapy for KOA on pain, stiffness, and physical function were conducted. Fourteen studies involving 841 KOA participants compared to other treatments were included. The methodological quality of most included RCTs was poor. The mean PEDro scale score was 6.6. The meta-analyses results showed that manual therapy had statistically significant effects on relieving pain (standardized mean difference, SMD = -0.61, 95% CI -0.95 to -0.28, P = 76%), stiffness (SMD = -0.58, 95% CI -0.95 to -0.21, P = 81%), improving physical function (SMD = -0.49, 95% CI -0.76 to -0.22, P = 65%), and total score (SMD = -0.56, 95% CI -0.78 to -0.35, P = 50%). But in the subgroups, manual therapy did not show significant improvements on stiffness and physical function when treatment duration was less than 4 weeks. And the long-term information for manual therapy was

Utilization of manual therapy to the lumbar spine in conjunction with traditional conservative care for individuals with bilateral lower extremity complex regional pain syndrome: A case series.

PubMed

Walston, Zachary; Hernandez, Luis; Yake, Dale

2018-06-06

Conservative therapies for complex regional pain syndrome (CRPS) have traditionally focused on exercise and desensitization techniques targeted at the involved extremity. The primary purpose of this case series is to report on the potential benefit of utilizing manual therapy to the lumbar spine in conjunction with traditional conservative care when treating patients with lower extremity CRPS. Two patients with the diagnosis of lower extremity CRPS were treated with manual therapy to the lumbar spine in conjunction with education, exercise, desensitization, and soft tissue techniques for the extremity. Patient 1 received 13 sessions over 6 weeks resulting in a 34-point improvement in oswestry disability index (ODI) and 35-point improvement in lower extremity functional scale (LEFS). Patient 2 received 21 sessions over 12 weeks resulting in a 28-point improvement in ODI and a 41-point improvement in LEFS. Both patients exhibited reductions in pain and clinically meaningful improvements in function. Manual therapies when applied to the lumbar spine in these patients as part of a comprehensive treatment plan resulted in improved spinal mobility, decreased pain, and reduction is distal referred symptoms. Although one cannot infer a cause and effect relationship from a case series, this report identifies meaningful clinical outcomes potentially associated with manual physical therapy to the lumbar spine for two patients with complex regional pain syndrome type 1.

Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial

PubMed Central

Bos, Ingeborg B C Korthals-de; Hoving, Jan L; van Tulder, Maurits W; Mölken, Maureen P M H Rutten-van; Adèr, Herman J; de Vet, Henrica C W; Koes, Bart W; Vondeling, Hindrik; Bouter, Lex M

2003-01-01

Objective To evaluate the cost effectiveness of physiotherapy, manual therapy, and care by a general practitioner for patients with neck pain. Design Economic evaluation alongside a randomised controlled trial. Setting Primary care. Participants 183 patients with neck pain for at least two weeks recruited by 42 general practitioners and randomly allocated to manual therapy (n=60, spinal mobilisation), physiotherapy (n=59, mainly exercise), or general practitioner care (n=64, counselling, education, and drugs). Main outcome measures Clinical outcomes were perceived recovery, intensity of pain, functional disability, and quality of life. Direct and indirect costs were measured by means of cost diaries that were kept by patients for one year. Differences in mean costs between groups, cost effectiveness, and cost utility ratios were evaluated by applying non-parametric bootstrapping techniques. Results The manual therapy group showed a faster improvement than the physiotherapy group and the general practitioner care group up to 26 weeks, but differences were negligible by follow up at 52 weeks. The total costs of manual therapy (€447; £273; $402) were around one third of the costs of physiotherapy (€1297) and general practitioner care (€1379). These differences were significant: P<0.01 for manual therapy versus physiotherapy and manual therapy versus general practitioner care and P=0.55 for general practitioner care versus physiotherapy. The cost effectiveness ratios and the cost utility ratios showed that manual therapy was less costly and more effective than physiotherapy or general practitioner care. Conclusions Manual therapy (spinal mobilisation) is more effective and less costly for treating neck pain than physiotherapy or care by a general practitioner. What is already known on this topicThe cost of treating neck pain is considerableMany conservative interventions are available, such as prescription drugs, yet their cost effectiveness has not been

MIT-MANUS: a workstation for manual therapy and training II

NASA Astrophysics Data System (ADS)

Hogan, Neville; Krebs, Hermano I.; Charnnarong, J.; Srikrishna, P.; Sharon, Andre

1993-03-01

This paper presents some recent work on the development of a workstation for teaching and therapy in manual and manipulative skills. The experimental workstation, MANUS, as well as the overall concept are described. State-of-the-art aspects of the workstation under development are introduced.

Diet manuals to practice manuals: the evolution of nutrition care.

PubMed

Chima, Cinda S

2007-02-01

Although the role of nutrition as a therapy for the sick has been recognized for centuries, the science of nutrition is a relatively young discipline. The first modern attempt to document and standardize appropriate nutrition care was the diet manual. The evolution from "diet manual" to "practice manual" is less a change in purpose than an expansion of scope. This paper reviews the history of diet manuals in the United States, focusing on the evolution of nutrition therapy and the transformation of diet manuals into practice manuals for nutrition care providers. Included is a practice-oriented summary of 7 diet manuals published by Cleveland Metropolitan General Hospital in Cleveland from 1939 to 1984, when the hospital began using nationally distributed practice manuals. These manuals exemplify changes in the practice of medicine and in the role of nutrition providers on the healthcare team. A review of the evolution of clinical decision-making as documented in diet and practice manuals reflects increasing rigor in referencing scientific evidence. Nutrition therapies that seem quaint to us now reflect the traditional origins of many medical practices that persist today. Knowledge of this history should motivate us to critically evaluate the research base that supports all aspects of nutrition therapy, develop protocols to assess practices that remain unexamined, and embrace the discipline of evidence-based practice.

Manual therapy for unsettled, distressed and excessively crying infants: a systematic review and meta-analyses

PubMed Central

Carnes, Dawn; Plunkett, Austin; Ellwood, Julie; Miles, Clare

2018-01-01

Objective To conduct a systematic review and meta-analyses to assess the effect of manual therapy interventions for healthy but unsettled, distressed and excessively crying infants and to provide information to help clinicians and parents inform decisions about care. Methods We reviewed published peer-reviewed primary research articles in the last 26 years from nine databases (Medline Ovid, Embase, Web of Science, Physiotherapy Evidence Database, Osteopathic Medicine Digital Repository, Cochrane (all databases), Index of Chiropractic Literature, Open Access Theses and Dissertations and Cumulative Index to Nursing and Allied Health Literature). Our inclusion criteria were: manual therapy (by regulated or registered professionals) of unsettled, distressed and excessively crying infants who were otherwise healthy and treated in a primary care setting. Outcomes of interest were: crying, feeding, sleep, parent–child relations, parent experience/satisfaction and parent-reported global change. Results Nineteen studies were selected for full review: seven randomised controlled trials, seven case series, three cohort studies, one service evaluation study and one qualitative study. We found moderate strength evidence for the effectiveness of manual therapy on: reduction in crying time (favourable: −1.27 hours per day (95% CI −2.19 to –0.36)), sleep (inconclusive), parent–child relations (inconclusive) and global improvement (no effect). The risk of reported adverse events was low: seven non-serious events per 1000 infants exposed to manual therapy (n=1308) and 110 per 1000 in those not exposed. Conclusions Some small benefits were found, but whether these are meaningful to parents remains unclear as does the mechanisms of action. Manual therapy appears relatively safe. PROSPERO registration number CRD42016037353. PMID:29371279

The effect of visual context on manual localization of remembered targets

NASA Technical Reports Server (NTRS)

Barry, S. R.; Bloomberg, J. J.; Huebner, W. P.

1997-01-01

This paper examines the contribution of egocentric cues and visual context to manual localization of remembered targets. Subjects pointed in the dark to the remembered position of a target previously viewed without or within a structured visual scene. Without a remembered visual context, subjects pointed to within 2 degrees of the target. The presence of a visual context with cues of straight ahead enhanced pointing performance to the remembered location of central but not off-center targets. Thus, visual context provides strong visual cues of target position and the relationship of body position to target location. Without a visual context, egocentric cues provide sufficient input for accurate pointing to remembered targets.

Targeted therapy in esophageal cancer.

PubMed

Zhang, Lei; Ma, Jiaojiao; Han, Yu; Liu, Jinqiang; Zhou, Wei; Hong, Liu; Fan, Daiming

2016-01-01

An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.

Manual therapy for unsettled, distressed and excessively crying infants: a systematic review and meta-analyses.

PubMed

Carnes, Dawn; Plunkett, Austin; Ellwood, Julie; Miles, Clare

2018-01-24

To conduct a systematic review and meta-analyses to assess the effect of manual therapy interventions for healthy but unsettled, distressed and excessively crying infants and to provide information to help clinicians and parents inform decisions about care. We reviewed published peer-reviewed primary research articles in the last 26 years from nine databases (Medline Ovid, Embase, Web of Science, Physiotherapy Evidence Database, Osteopathic Medicine Digital Repository , Cochrane (all databases), Index of Chiropractic Literature, Open Access Theses and Dissertations and Cumulative Index to Nursing and Allied Health Literature). Our inclusion criteria were: manual therapy (by regulated or registered professionals) of unsettled, distressed and excessively crying infants who were otherwise healthy and treated in a primary care setting. Outcomes of interest were: crying, feeding, sleep, parent-child relations, parent experience/satisfaction and parent-reported global change. Nineteen studies were selected for full review: seven randomised controlled trials, seven case series, three cohort studies, one service evaluation study and one qualitative study.We found moderate strength evidence for the effectiveness of manual therapy on: reduction in crying time (favourable: -1.27 hours per day (95% CI -2.19 to -0.36)), sleep (inconclusive), parent-child relations (inconclusive) and global improvement (no effect). The risk of reported adverse events was low: seven non-serious events per 1000 infants exposed to manual therapy (n=1308) and 110 per 1000 in those not exposed. Some small benefits were found, but whether these are meaningful to parents remains unclear as does the mechanisms of action. Manual therapy appears relatively safe. CRD42016037353. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Targeted therapies: a nursing perspective.

PubMed

Kay, Polly

2006-02-01

To review the development of targeted therapies and the biology of relevant therapeutic targets. To analyze the relevance of targeted agents as part of current clinical practice. Research articles. Several targeted agents are now available for clinical use. Their mechanisms of action are more specific against tumor cells than traditional cytotoxics. Monotherapy regimens based on targeted agents tend to be better tolerated than chemotherapy, and most combination regimens with targeted agents have proven feasible. Their availability has greatly expanded cancer treatment options, especially for chemorefractory patients. Nurses involved in the care of patients with cancer can benefit from an increased understanding of targeted therapies, including their mechanisms of action, their efficacy profile, as well as prophylaxis and management of adverse events and administration procedures.

Effectiveness of manual therapy versus surgery in pain processing due to carpal tunnel syndrome: A randomized clinical trial.

PubMed

Fernández-de-Las-Peñas, C; Cleland, J; Palacios-Ceña, M; Fuensalida-Novo, S; Alonso-Blanco, C; Pareja, J A; Alburquerque-Sendín, F

2017-08-01

People with carpal tunnel syndrome (CTS) exhibit widespread pressure pain and thermal pain hypersensitivity as a manifestation of central sensitization. The aim of our study was to compare the effectiveness of manual therapy versus surgery for improving pain and nociceptive gain processing in people with CTS. The trial was conducted at a local regional Hospital in Madrid, Spain from August 2014 to February 2015. In this randomized parallel-group, blinded, clinical trial, 100 women with CTS were randomly allocated to either manual therapy (n = 50), who received three sessions (once/week) of manual therapies including desensitization manoeuvres of the central nervous system, or surgical intervention (n = 50) group. Outcomes including pressure pain thresholds (PPT), thermal pain thresholds (HPT or CPT), and pain intensity which were assessed at baseline, and 3, 6, 9 and 12 months after the intervention by an assessor unaware of group assignment. Analysis was by intention to treat with mixed ANCOVAs adjusted for baseline scores. At 12 months, 95 women completed the follow-up. Patients receiving manual therapy exhibited higher increases in PPT over the carpal tunnel at 3, 6 and 9 months (all, p < 0.01) and higher decrease of pain intensity at 3 month follow-up (p < 0.001) than those receiving surgery. No significant differences were observed between groups for the remaining outcomes. Manual therapy and surgery have similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with CTS. Neither manual therapy nor surgery resulted in changes in thermal pain sensitivity. The current study found that manual therapy and surgery exhibited similar effects on decreasing widespread pressure pain sensitivity and pain intensity in women with carpal tunnel syndrome at medium- and long-term follow-ups investigating changes in nociceptive gain processing after treatment in carpal tunnel syndrome. © 2017 European Pain Federation - EFIC®.

Validation of Placebo in a Manual Therapy Randomized Controlled Trial

PubMed Central

Chaibi, Aleksander; Šaltytė Benth, Jūratė; Bjørn Russell, Michael

2015-01-01

At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment (“yes” or “no”) and how strongly they believed that active treatment was received (numeric rating scale 0–10). The outcome measures included the rate of successful blinding and the certitude of the participants’ beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months. PMID:26145718

Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial.

PubMed

Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

2009-05-21

Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology.Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. http://www.clinicaltrials.gov identifier NCT00847769.

Periosteal Electrical Dry Needling as an Adjunct to Exercise and Manual Therapy for Knee Osteoarthritis: A Multi-Center Randomized Clinical Trial.

PubMed

Dunning, James; Butts, Raymond; Young, Ian; Mourad, Firas; Galante, Victoria; Bliton, Paul; Tanner, Michelle; Fernández-de-Las-Peñas, César

2018-05-28

To compare the effects of adding electrical dry needling into a manual therapy and exercise program on pain, stiffness, function, and disability in individuals with painful knee osteoarthritis (OA). Two hundred and forty-two participants (n=242) with painful knee OA were randomized to receive 6 weeks of electrical dry needling, manual therapy and exercise (n=121) or manual therapy and exercise (n=121). The primary outcome was related-disability as assessed by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at 3 months. Individuals receiving the combination of electrical dry needling, manual therapy and exercise experienced significantly greater improvements in related-disability (WOMAC: F=35.504; P<0.001) than those receiving manual therapy and exercise alone at 6 weeks and 3 months. Patients receiving electrical dry needling were 1.7 times more likely to have completely stopped taking medication for their pain at 3 months than individuals receiving manual therapy and exercise (OR: 1.6; 95%CI: 1.24-2.01; P=0.001). Based on the cutoff score of +5 on the Global Rating of Change (GROC), significantly (X =14.887; P<0.001) more patients (n=91, 75%) within the dry needling group achieved a successful outcome compared to the manual therapy and exercise group (n=22, 18%) at 3 months. Effect sizes were large (SMD>0.82) for all outcome measures in favor of the electrical dry needling group at 3 months. The inclusion of electrical dry needling into a manual therapy and exercise program was more effective for improving pain, function and related-disability than the application of manual therapy and exercise alone in individuals with painful knee OA. Therapy, Level 1b. Prospectively registered February 10, 2015 on http://www.clinicaltrials.gov (NCT02373631)This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share

Clinical presentation and manual therapy for lower quadrant musculoskeletal conditions.

PubMed

Courtney, Carol A; Clark, Jeffrey D; Duncombe, Alison M; O'Hearn, Michael A

2011-11-01

Chronic lower quadrant injuries constitute a significant percentage of the musculoskeletal cases seen by clinicians. While impairments may vary, pain is often the factor that compels the patient to seek medical attention. Traumatic injury from sport is one cause of progressive chronic joint pain, particularly in the lower quarter. Recent studies have demonstrated the presence of peripheral and central sensitization mechanisms in different lower quadrant pain syndromes, such as lumbar spine related leg pain, osteoarthritis of the knee, and following acute injuries such as lateral ankle sprain and anterior cruciate ligament rupture. Proper management of lower quarter conditions should include assessment of balance and gait as increasing pain and chronicity may lead to altered gait patterns and falls. In addition, quantitative sensory testing may provide insight into pain mechanisms which affect management and prognosis of musculoskeletal conditions. Studies have demonstrated analgesic effects and modulation of spinal excitability with use of manual therapy techniques, with clinical outcomes of improved gait and functional ability. This paper will discuss the evidence which supports the use of manual therapy for lower quarter musculoskeletal dysfunction.

Three combinations of manual therapy techniques within naprapathy in the treatment of neck and/or back pain: a randomized controlled trial.

PubMed

Paanalahti, Kari; Holm, Lena W; Nordin, Margareta; Höijer, Jonas; Lyander, Jessica; Asker, Martin; Skillgate, Eva

2016-04-23

Manual therapy as spinal manipulation, spinal mobilization, stretching and massage are common treatment methods for neck and back pain. The objective was to compare the treatment effect on pain intensity, pain related disability and perceived recovery from a) naprapathic manual therapy (spinal manipulation, spinal mobilization, stretching and massage) to b) naprapathic manual therapy without spinal manipulation and to c) naprapathic manual therapy without stretching for male and female patients seeking care for back and/or neck pain. Participants were recruited among patients, ages 18-65, seeking care at the educational clinic of Naprapathögskolan - the Scandinavian College of Naprapathic Manual Medicine in Stockholm. The patients (n = 1057) were randomized to one of three treatment arms a) manual therapy (i.e. spinal manipulation, spinal mobilization, stretching and massage), b) manual therapy excluding spinal manipulation and c) manual therapy excluding stretching. The primary outcomes were minimal clinically important improvement in pain intensity and pain related disability. Treatments were provided by naprapath students in the seventh semester of eight total semesters. Generalized estimating equations and logistic regression were used to examine the association between the treatments and the outcomes. At 12 weeks follow-up, 64% had a minimal clinically important improvement in pain intensity and 42% in pain related disability. The corresponding chances to be improved at the 52 weeks follow-up were 58% and 40% respectively. No systematic differences in effect when excluding spinal manipulation and stretching respectively from the treatment were found over 1 year follow-up, concerning minimal clinically important improvement in pain intensity (p = 0.41) and pain related disability (p = 0.85) and perceived recovery (p = 0.98). Neither were there disparities in effect when male and female patients were analyzed separately. The effect of manual therapy for male

Psychodynamic psychotherapy for social phobia: a treatment manual based on supportive-expressive therapy.

PubMed

Leichsenring, Falk; Beutel, Manfred; Leibing, Eric

2007-01-01

Social phobia is a very frequent mental disorder characterized by an early onset, a chronic unremitting course, severe psychosocial impairments and high socioeconomic costs. To date, no manual for the psychodynamic treatment of social phobia exists. After a brief description of the disorder, a manual for a short-term psychodynamic treatment of social phobia is presented. The treatment is based on Luborsky s supportive-expressive (SE) therapy, which is complemented by treatment elements specific to social phobia. The treatment includes the characteristic elements of SE therapy, that is, setting goals, focus on the Core Conflictual Relationship Theme (CCRT) associated with the patient s symptoms, interpretive interventions to enhance insight into the CCRT, and supportive interventions, in particular fostering a helping alliance. In order to tailor the treatment more specifically to social phobia, treatment elements have been added, for example informing the patient about the disorder and the treatment, a specific focus on shame and on unrealistic demands, and encouraging the patient to confront anxiety-producing situations. More directive interventions are included as well, such as specific prescriptions to stop persisting self-devaluations. The treatment manual is presently being used in a large-scale randomized controlled multicenter study comparing short-term psychodynamic psychotherapy and cognitive-behavioral therapy in the treatment of social phobia.

Targeted therapies for cancer

MedlinePlus

Targeted therapies are promising new treatments, but they have limitations. Cancer cells can become resistant to these drugs. The target sometimes changes, so the treatment no longer works. The cancer may find a different way to grow and survive that ...

Multimodal manual therapy vs. pharmacological care for management of tension type headache: A meta-analysis of randomized trials.

PubMed

Mesa-Jiménez, Juan A; Lozano-López, Cristina; Angulo-Díaz-Parreño, Santiago; Rodríguez-Fernández, Ángel L; De-la-Hoz-Aizpurua, Jose L; Fernández-de-Las-Peñas, Cesar

2015-12-01

Manual therapies are generally requested by patients with tension type headache. To compare the efficacy of multimodal manual therapy vs. pharmacological care for the management of tension type headache pain by conducting a meta-analysis of randomized controlled trials. PubMed, MEDLINE, EMBASE, AMED, CINAHL, EBSCO, Cochrane Database of Systematic Reviews, Cochrane Collaboration Trials Register, PEDro and SCOPUS were searched from their inception until June 2014. All randomized controlled trials comparing any manual therapy vs. medication care for treating tension type headache adults were included. Data were extracted and methodological quality assessed independently by two reviewers. We pooled headache frequency as the main outcome and also intensity and duration. The weighted mean difference between manual therapy and pharmacological care was used to determine effect sizes. Five randomized controlled trials met our inclusion criteria and were included in the meta-analysis. Pooled analyses found that manual therapies were more effective than pharmacological care in reducing frequency (weighted mean difference -0.8036, 95% confidence interval -1.66 to -0.44; three trials), intensity (weighted mean difference -0.5974, 95% confidence interval -0.8875 to -0.3073; five trials) and duration (weighted mean difference -0.5558, 95% confidence interval -0.9124 to -0.1992; three trials) of the headache immediately after treatment. No differences were found at longer follow-up for headache intensity (weighted mean difference -0.3498, 95% confidence interval -1.106 to 0.407; three trials). Manual therapies were associated with moderate effectiveness at short term, but similar effectiveness at longer follow-up for reducing headache frequency, intensity and duration in tension type headache than pharmacological medical drug care. However, due to the heterogeneity of the interventions, these results should be considered with caution at this stage. © International Headache

Ultrasound-Guided Application of Percutaneous Electrolysis as an Adjunct to Exercise and Manual Therapy for Subacromial Pain Syndrome: a Randomized Clinical Trial.

PubMed

de-Miguel-Valtierra, Lorena; Salom-Moreno, Jaime; Fernández-de-Las-Peñas, César; Cleland, Joshua A; Arias-Buría, José L

2018-05-16

This randomized clinical trial compared the effects of adding US-guided percutaneous electrolysis into a program consisting of manual therapy and exercise on pain, related-disability, function and pressure sensitivity in subacromial pain syndrome. Fifty patients with subacromial pain syndrome were randomized into manual therapy and exercise or percutaneous electrolysis group. All patients received the same manual therapy and exercise program, one session per week for 5 consecutive weeks. Patients assigned to the electrolysis group also received the application of percutaneous electrolysis at each session. The primary outcome was Disabilities of the Arm, Shoulder and Hand (DASH). Secondary outcomes included pain, function (Shoulder Pain and Disability Index-SPADI) pressure pain thresholds (PPTs) and Global Rating of Change (GROC). They were assessed at baseline, post-treatment, and 3, and 6 months after treatment. Both groups showed similar improvements in the primary outcome (DASH) at all follow-ups (P=0.051). Subjects receiving manual therapy, exercise, and percutaneous electrolysis showed significantly greater changes in shoulder pain (P<0.001) and SPADI (P<0.001) than those receiving manual therapy and exercise alone at all follow-ups. Effect sizes were large (SMD>0.91) for shoulder pain and function at 3 and 6 months in favour of the percutaneous electrolysis group. No between-groups differences in PPT were found. The current clinical trial found that the inclusion of US-guided percutaneous electrolysis in combination with manual therapy and exercise resulted in no significant differences for related-disability (DASH) than the application of manual therapy and exercise alone in patients with subacromial pain syndrome. Nevertheless, differences were reported for some secondary outcomes such as shoulder pain and function (SPADI). Whether or not these effects are reliable should be addressed in future studies Perspective This study found that the inclusion of US

Identification of potential neuromotor mechanisms of manual therapy in patients with musculoskeletal disablement: rationale and description of a clinical trial

PubMed Central

Fisher, Beth E; Davenport, Todd E; Kulig, Kornelia; Wu, Allan D

2009-01-01

Background Many health care practitioners use a variety of hands-on treatments to improve symptoms and disablement in patients with musculoskeletal pathology. Research to date indirectly suggests a potentially broad effect of manual therapy on the neuromotor processing of functional behavior within the supraspinal central nervous system (CNS) in a manner that may be independent of modification at the level of local spinal circuits. However, the effect of treatment speed, as well as the specific mechanism and locus of CNS changes, remain unclear. Methods/Design We developed a placebo-controlled, randomized study to test the hypothesis that manual therapy procedures directed to the talocrural joint in individuals with post-acute ankle sprain induce a change in corticospinal excitability that is relevant to improve the performance of lower extremity functional behavior. Discussion This study is designed to identify potential neuromotor changes associated with manual therapy procedures directed to the appendicular skeleton, compare the relative effect of treatment speed on potential neuromotor effects of manual therapy procedures, and determine the behavioral relevance of potential neuromotor effects of manual therapy procedures. Trial Registration identifier NCT00847769. PMID:19460169

Manual therapy is an effective treatment for frozen shoulder in diabetics: an observational study.

PubMed

Düzgün, Irem; Baltaci, Gül; Atay, Ozgür Ahmet

2012-01-01

This study aims to compare the efficacy of manual therapy in the frozen shoulder patients with or without diabetes mellitus. Between May 2006 and January 2008, 50 patients (10 males, 40 females; mean age 52 ± 10 years; range 40 to 65 years) orthopedic surgeons referred to the Sports Physiotherapy Unit were included in the study. The patients were divided into two groups, including patients with primary frozen shoulder with type II diabetes mellitus (n=12) and non diabetics (n=38). All patients underwent a rehabilitation program including cold application, manual therapy and exercises twice a week. A total of 16 treatment sessions were performed. The most important part of the manual therapy included scapular mobilization and posterior capsule stretching. The range of motion was measured by goniometry. Functional activity status was assessed by Constant's score. The pain level was evaluated by visual analog scale, while muscle strength was evaluated by hand-held dynamometer. Student t-test was used to compare between the parameters of groups, while Paired sample t-test was used to compare pre- and post-treatment parameters of the patients. The range of motion, functional activity status and muscular strength were improved and the pain level was reduced after rehabilitation in all of the patients in both groups (p<0.05). There was no difference in duration of the treatment between the groups (p>0.05). There were no differences in range of motion, functional activity status, pain level, and muscle strength before and after rehabilitation between the groups (p>0.05). Manual therapy approaches may be safely applied in diabetic patients with frozen shoulder.

New targeted therapies in pancreatic cancer.

PubMed

Seicean, Andrada; Petrusel, Livia; Seicean, Radu

2015-05-28

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Novel use of a manual therapy technique and management of a patient with peroneal tendinopathy: a case report.

PubMed

Hensley, Craig P; Kavchak, Alicia J Emerson

2012-02-01

Peroneal tendinopathy is an uncommon but underappreciated source of lateral hindfoot pain and dysfunction. There is a paucity of literature describing optimal intervention for those suffering with pain secondary to peroneal tendinopathy. The purpose of this case report is to describe the evaluation and treatment incorporating manual therapy and therapeutic exercise for a patient diagnosed with peroneal tendinopathy. The patient was a 50 year-old female with a history of chronic lateral ankle pain and whose presentation was consistent with peroneal tendinopathy. Despite attempts to improve pain and function with over-the-counter orthotics, manual therapy to a hypomobile talocrural joint, and strengthening of the peroneal tendons, successful response was not reported until a lateral calcaneal glide was added. Improvement in impairments (pain, talocrural dorsiflexion, unilateral heel raises, and Star Excursion Balance Test) and function (Lower Extremity Functional Scale and Global Rating of Change), were observed over a course of eight visits. The patient was able to return to work and her recreational work out routine without limitations. In conclusion a successful physical therapy intervention for a patient with peroneal tendinopathy included a unique manual therapy technique, the lateral calcaneal glide, in conjunction with other manual therapy techniques and a structured home exercise program. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical outcomes following manual physical therapy and exercise for hip osteoarthritis: A case series.

PubMed

MacDonald, Cameron W; Whitman, Julie M; Cleland, Joshua A; Smith, Marcia; Hoeksma, Hugo L

2006-08-01

Case series describing the outcomes of individual patients with hip osteoarthritis treated with manual physical therapy and exercise. Seven patients referred to physical therapy with hip osteoarthritis and/or hip pain were included in this case series. All patients were treated with manual physical therapy followed by exercises to maximize strength and range of motion. Six of 7 patients completed a Harris Hip Score at initial examination and discharge from physical therapy, and 1 patient completed a Global Rating of Change Scale at discharge. Three males and 4 females with a median age of 62 years (range, 52-80 years) and median duration of symptoms of 9 months (range, 2-60 months) participated in this case series. The median number of physical therapy sessions attended was 5 (range, 4-12). The median increase in total passive range of motion of the hip was 82 degrees (range, 70 degrees-86 degrees). The median improvement on the Harris Hip Score was 25 points (range, 15-38 points). The single patient who completed the Global Rating of Change Scale at discharge reported being "a great deal better." Numeric pain rating scores decreased by a mean of 5 points (range, 2-7 points) on 0-to-10-point scale. All patients exhibited reductions in pain and increases in passive range of motion, as well as a clinically meaningful improvement in function. Although we can not infer a cause and effect relationship from a case series, the outcomes with these patients are similar to others reported in the literature that have demonstrated superior clinical outcomes associated with manual physical therapy and exercise for hip osteoarthritis compared to exercise alone.

Strength training alone, exercise therapy alone, and exercise therapy with passive manual mobilisation each reduce pain and disability in people with knee osteoarthritis: a systematic review.

PubMed

Jansen, Mariette J; Viechtbauer, Wolfgang; Lenssen, Antoine F; Hendriks, Erik J M; de Bie, Rob A

2011-01-01

What are the effects of strength training alone, exercise therapy alone, and exercise with additional passive manual mobilisation on pain and function in people with knee osteoarthritis compared to control? What are the effects of these interventions relative to each other? A meta-analysis of randomised controlled trials. Adults with osteoarthritis of the knee. INTERVENTION TYPES: Strength training alone, exercise therapy alone (combination of strength training with active range of motion exercises and aerobic activity), or exercise with additional passive manual mobilisation, versus any non-exercise control. Comparisons between the three interventions were also sought. The primary outcome measures were pain and physical function. 12 trials compared one of the interventions against control. The effect size on pain was 0.38 (95% CI 0.23 to 0.54) for strength training, 0.34 (95% CI 0.19 to 0.49) for exercise, and 0.69 (95% CI 0.42 to 0.96) for exercise plus manual mobilisation. Each intervention also improved physical function significantly. No randomised comparisons of the three interventions were identified. However, meta-regression indicated that exercise plus manual mobilisations improved pain significantly more than exercise alone (p = 0.03). The remaining comparisons between the three interventions for pain and physical function were not significant. Exercise therapy plus manual mobilisation showed a moderate effect size on pain compared to the small effect sizes for strength training or exercise therapy alone. To achieve better pain relief in patients with knee osteoarthritis physiotherapists or manual therapists might consider adding manual mobilisation to optimise supervised active exercise programs. Copyright © 2011 Australian Physiotherapy Association. Published by .. All rights reserved.

The functional manual therapy intervention in infants with nonsynostotic plagiocephaly: a pilot study.

PubMed

Billi, Mariangela; Greco, Angelo; Colonneli, Paola; Volpi, Giordana; Valente, Donatella; Galeoto, Giovanni

2017-10-25

To document the evolution of cranial asymmetries in infants with signs of nonsynostotic occipital plagiocephaly (NSOP) who were undergo to many functional manual therapy treatments (in addition to the standard positioning recommendations) as well as to determine the feasibility of this methodology to conduct an outcome research investigating the impact of this intervention for infants with NSOP. Pilot clinical standardization project using pre-post design in which 10 infants participated. Nine infants presented an initial Oblique Diameter Difference Index (ODDI) over 104%, three an initial Ear Deviation Index (EDI) over 4%, and three a Cranial Proportional Index (CPI) over 90%. Infants received three functional manual therapy treatments for week during the first month of intervention and two ones for week during the second month. Plagiocephalometric measurememts were administered at the first assessment pre-intervention (T0), after 30 days (+/-5) (T1) and at a third time after 60 days (+/5) of treatment (T2). 9/10 participants showed a significant decrease in ODDI under 104% between T0 and T2 assessments. 5/10 infants showed an EDI under 4%, and 3/10 showed a value about 0%. 3/10 maintained their CPI over 90% with a considerable decrease. These clinical findings support the hypothesis that functional manual therapy treatments contribute to the improvement of cranial asymmetries in infants younger than 6.5 months old presenting with NSOP.

Adherence and competence in two manual-guided therapies for co-occurring substance use and posttraumatic stress disorders: clinician factors and patient outcomes.

PubMed

Meier, Andrea; McGovern, Mark P; Lambert-Harris, Chantal; McLeman, Bethany; Franklin, Anna; Saunders, Elizabeth C; Xie, Haiyi

2015-01-01

The challenges of implementing and sustaining evidence-based therapies into routine practice have been well-documented. This study examines the relationship among clinician factors, quality of therapy delivery, and patient outcomes. Within a randomized controlled trial, 121 patients with current co-occurring substance use and posttraumatic stress disorders were allocated to receive either manualized Integrated Cognitive Behavioral Therapy (ICBT) or Individual Addiction Counseling (IAC). Twenty-two clinicians from seven addiction treatment programs were trained and supervised to deliver both therapies. Clinician characteristics were assessed at baseline; clinician adherence and competence were assessed over the course of delivering both therapies; and patient outcomes were measured at baseline and 6-month follow-up. Although ICBT was delivered at acceptable levels, clinicians were significantly more adherent to IAC (p < 0.05). At session 1, clinical female gender (p < 0.05) and lower education level (p < 0.05) were predictive of increased clinician adherence and competence across both therapies. Adherence and competence at session 1 in either therapy were significantly predictive of positive patient outcomes. ICBT adherence (p < 0.05) and competence (p < 0.01) were predictive of PTSD symptom reduction, whereas IAC adherence (p < 0.01) and competence (p < 0.01) were associated with decreased drug problem severity. The differential impact of adherence and competence for both therapy types is consistent with their purported primary target: ICBT for PTSD and IAC for substance use. These findings also suggest the benefits of considering clinician factors when implementing manual-guided therapies. Future research should focus on diverse clinician samples, randomization of clinicians to therapy type, and prospective designs to evaluate models of supervision and quality monitoring.

Developing a Manualized Occupational Therapy Diabetes Management Intervention: Resilient, Empowered, Active Living With Diabetes

PubMed Central

Pyatak, Elizabeth A.; Carandang, Kristine; Davis, Shain

2016-01-01

This article reports on the development of a manualized occupational therapy intervention for diabetes management. An initial theoretical framework and core content areas for a Stage 1 intervention manual were developed based on an in-depth needs assessment and review of existing literature. After evaluation by a panel of experts and completion of a feasibility study, the intervention was revised into a Stage 2 manual in preparation for a randomized study evaluating the intervention’s efficacy. In developing the initial manual, we delineated core theoretical principles to allow for flexible application and tailoring of the intervention’s content areas. Expert panel feedback and feasibility study results led to changes to the intervention structure and content as we developed the Stage 2 manual. Through describing this process, we illustrate the dynamic evolution of intervention manuals, which undergo revisions due to both theoretical and practical considerations at each stage of the research-to-clinical practice pipeline. PMID:26594741

Developing a Manualized Occupational Therapy Diabetes Management Intervention: Resilient, Empowered, Active Living With Diabetes.

PubMed

Pyatak, Elizabeth A; Carandang, Kristine; Davis, Shain

2015-07-01

This article reports on the development of a manualized occupational therapy intervention for diabetes management. An initial theoretical framework and core content areas for a Stage I intervention manual were developed based on an in-depth needs assessment and review of existing literature. After evaluation by a panel of experts and completion of a feasibility study, the intervention was revised into a Stage 2 manual in preparation for a randomized study evaluating the intervention's efficacy. In developing the initial manual, we delineated core theoretical principles to allow for flexible application and tailoring of the intervention's content areas. Expert panel feedback and feasibility study results led to changes to the intervention structure and content as we developed the Stage 2 manual. Through describing this process, we illustrate the dynamic evolution of intervention manuals, which undergo revisions due to both theoretical and practical considerations at each stage of the research-to-clinical practice pipeline.

Adverse events after manual therapy among patients seeking care for neck and/or back pain: a randomized controlled trial.

PubMed

Paanalahti, Kari; Holm, Lena W; Nordin, Margareta; Asker, Martin; Lyander, Jessica; Skillgate, Eva

2014-03-12

The safety of the manual treatment techniques such as spinal manipulation has been discussed and there is a need for more information about potential adverse events after manual therapy. The aim of this randomized controlled trial was to investigate differences in occurrence of adverse events between three different combinations of manual treatment techniques used by manual therapists (i.e. chiropractors, naprapaths, osteopaths, physicians and physiotherapists) for patients seeking care for back and/or neck pain. In addition women and men were compared regarding the occurrence of adverse events. Participants were recruited among patients, ages 18-65, seeking care at the educational clinic of the Scandinavian College of Naprapathic Manual Medicine in Stockholm. The patients (n = 767) were randomized to one of three treatment arms 1) manual therapy (i.e. spinal manipulation, spinal mobilization, stretching and massage) (n = 249), 2) manual therapy excluding spinal manipulation (n = 258) and 3) manual therapy excluding stretching (n = 260). Treatments were provided by students in the seventh semester of total eight. Adverse events were measured with a questionnaire after each return visit and categorized in to five levels; 1) short minor, 2) long minor, 3) short moderate, 4) long moderate and 5) serious adverse events, based on the duration and/or severity of the event. Generalized estimating equations were used to examine the association between adverse event and treatments arms. The most common adverse events were soreness in muscles, increased pain and stiffness. No differences were found between the treatment arms concerning the occurrence of adverse event. Fifty-one percent of patients, who received at least three treatments, experienced at least one adverse event after one or more visits. Women more often had short moderate adverse events (OR = 2.19 (95% CI: 1.52-3.15)), and long moderate adverse events (OR = 2.49 (95% CI: 1.77-3.52)) compared to men. Adverse

Manual Physical Therapy Versus Surgery for Carpal Tunnel Syndrome: A Randomized Parallel-Group Trial.

PubMed

Fernández-de-Las Peñas, César; Ortega-Santiago, Ricardo; de la Llave-Rincón, Ana I; Martínez-Perez, Almudena; Fahandezh-Saddi Díaz, Homid; Martínez-Martín, Javier; Pareja, Juan A; Cuadrado-Pérez, Maria L

2015-11-01

This randomized clinical trial investigated the effectiveness of surgery compared with physical therapy consisting of manual therapies including desensitization maneuvers in carpal tunnel syndrome (CTS). The setting was a public hospital and 2 physical therapy practices in Madrid, Spain. One hundred twenty women with CTS were enrolled between February 2013 and January 2014, with 1-year follow-up completed in January 2015. Interventions consisted of 3 sessions of manual therapies including desensitization maneuvers of the central nervous system (physical therapy group, n = 60) or decompression/release of the carpal tunnel (surgical group, n = 60). The primary outcome was pain intensity (mean pain and the worst pain), and secondary outcomes included functional status and symptoms severity subscales of the Boston Carpal Tunnel Questionnaire and the self-perceived improvement. They were assessed at baseline and 1, 3, 6, and 12 months by a blinded assessor. Analysis was by intention to treat. At 12 months, 111 (92%) women completed the follow-up (55/60 physical therapy, 56/60 surgery). Adjusted analyses showed an advantage (all, P < .01) for physical therapy at 1 and 3 months in mean pain (Δ -2.0 [95% confidence interval (CI) -2.8 to -1.2]/-1.3 [95% CI -2.1 to -.6]), the worst pain (Δ -2.9 [-4.0 to -2.0]/-2.0 [-3.0 to -.9]), and function (Δ -.8 [-1.0 to -.6]/-.3 [-.5 to -.1]), respectively. Changes in pain and function were similar between the groups at 6 and 12 months. The 2 groups had similar improvements in the symptoms severity subscale of the Boston Carpal Tunnel Questionnaire at all follow-ups. In women with CTS, physical therapy may result in similar outcomes on pain and function to surgery. http://www.clinicaltrials.gov, ClinicalTrials.gov, NCT01789645. This study found that surgery and physical manual therapies including desensitization maneuvers of the central nervous system were similarly effective at medium-term and long-term follow-ups for improving pain

Comparison between effectiveness of Mechanical and Manual Traction combined with mobilization and exercise therapy in Patients with Cervical Radiculopathy.

PubMed

Bukhari, Syed Rehan Iftikhar; Shakil-Ur-Rehman, Syed; Ahmad, Shakeel; Naeem, Aamer

2016-01-01

Cervical radiculopathy is a common neuro-musculo-skeletal disorder causing pain and disability. Traction is part of the evidence based manual physical therapy management due to its mechanical nature, type of traction and parameters related to its applicability and are still to be explored more through research. Our objective was to determine the Effects of Mechanical versus Manual Traction in Manual Physical Therapy combined with segmental mobilization and exercise therapy in the physical therapy management of Patients with Cervical Radiculopathy. This randomized control trial was conducted at department of physical therapy and rehabilitation, Rathore Hospital Faisalabad, from February to July 2015. Inclusion criteria were both male and female patients with evident symptoms of cervical spine radiculopathy and age ranged between 20-70 years. The exclusion criteria were Patients with history of trauma, neck pain without radiculopathy, aged less than 20 and more than 70. A total of 72 patients with cervical radiculopathy were screened out as per the inclusion criteria, 42 patients were randomly selected and placed into two groups by toss and trial method, and only 36 patients completed the study, while 6 dropped out. The mechanical traction was applied in group A and manual traction in group B along with common intervention of segmental mobilization and exercise therapy in both groups for 6 weeks. The patient's outcomes were assessed by self reported NPRS and NDI at the baseline and after completion of 06 weeks exercise program at 3 days per week. The data was analyzed through SPSS version-21, and paired T test was applied at 95% level significance to determine the statistical deference between two groups. Clinically the group of patients treated with mechanical traction managed pain (mean pre 6.26, mean post 1.43), and disability (mean pre 24.43 and mean post 7.26) more effectively as compared with the group of patients treated with manual traction (Pain mean pre 6

Manually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: an early experience.

PubMed

Shoji, Sunao; Hiraiwa, Shinichiro; Endo, Jun; Hashida, Kazunobu; Tomonaga, Tetsuro; Nakano, Mayura; Sugiyama, Tomoko; Tajiri, Takuma; Terachi, Toshiro; Uchida, Toyoaki

2015-02-01

To report our early experience with manually controlled targeted biopsy with real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion images for the diagnosis of prostate cancer. A total of 20 consecutive patients suspicious of prostate cancer at the multiparametric magnetic resonance imaging scan were recruited prospectively. Targeted biopsies were carried out for each cancer-suspicious lesion, and 12 systematic biopsies using the BioJet system. Pathological findings of targeted and systematic biopsies were analyzed. The median age of the patients was 70 years (range 52-83 years). The median preoperative prostate-specific antigen value was 7.4 ng/mL (range 3.54-19.9 ng/mL). Median preoperative prostate volume was 38 mL (range 24-68 mL). The number of cancer-detected cases was 14 (70%). The median Gleason score was 6.5 (range 6-8). Cancer-detected rates of the systematic and targeted biopsy cores were 6.7 and 31.8%, respectively (P < 0.0001). In six patients who underwent radical prostatectomy, the geographic locations and pathological grades of clinically significant cancers and index lesions corresponded to the pathological results of the targeted biopsies. Prostate cancers detected by targeted biopsies with manually controlled targeted biopsy using real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion imaging have significantly higher grades and longer length compared with those detected by systematic biopsies. Further studies and comparison with the pathological findings of whole-gland specimens have the potential to determine the role of this biopsy methodology in patients selected for focal therapy and those under active surveillance. © 2014 The Japanese Urological Association.

Ankle sprains: combination of manual therapy and supervised exercise leads to better recovery.

PubMed

2013-01-01

Ankle sprains often occur when running, walking on uneven ground, or jumping. Usually, people are told to rest, elevate the foot, apply ice, and use an elastic wrap to reduce swelling. This treatment is typically followed by exercises that can be performed at home. Although the pain and swelling usually improve quickly, more than 70% of people who sprain their ankles continue to have problems with them and up to 80% will sprain their ankles again. This suggests that it is important to better care for ankle sprains. One option is manual therapy, where the therapist moves the ankle and surrounding joints to help restore normal joint movement. A research report published in the July 2013 issue of JOSPT examines and compares the outcomes of a home exercise program with a more involved treatment program that includes manual therapy and supervised exercises.

Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted therapies for lung cancer

PubMed Central

Savas, Peter; Hughes, Brett

2013-01-01

Advances in the treatment of non-small cell lung cancer (NSCLC) over the last decade have predominantly involved the development of therapies directed at molecular targets such as mutations in the epidermal growth factor receptor (EGFR) or rearrangements in the anaplastic lymphoma kinase (ALK) gene. Other targets have been discovered at low frequency, with multiple agents approved or in development for treatment of these rare molecular subtypes. The tumour microenvironment has also provided opportunities for therapies targeting angiogenesis and the host immune response. This review will provide an overview of current targeted therapies in NSCLC and promising treatment approaches on the horizon. PMID:24163750

Orofacial manual therapy improves cervical movement impairment associated with headache and features of temporomandibular dysfunction: a randomized controlled trial.

PubMed

von Piekartz, Harry; Hall, Toby

2013-08-01

There is evidence that temporomandibular disorder (TMD) may be a contributing factor to cervicogenic headache (CGH), in part because of the influence of dysfunction of the temporomandibular joint on the cervical spine. The purpose of this randomized controlled trial was to determine whether orofacial treatment in addition to cervical manual therapy, was more effective than cervical manual therapy alone on measures of cervical movement impairment in patients with features of CGH and signs of TMD. In this study, 43 patients (27 women) with headache for more than 3-months and with some features of CGH and signs of TMD were randomly assigned to receive either cervical manual therapy (usual care) or orofacial manual therapy to address TMD in addition to usual care. Subjects were assessed at baseline, after 6 treatment sessions (3-months), and at 6-months follow-up. 38 subjects (25 female) completed all analysis at 6-months follow-up. The outcome criteria were: cervical range of movement (including the C1-2 flexion-rotation test) and manual examination of the upper 3 cervical vertebra. The group that received orofacial treatment in addition to usual care showed significant reduction in all aspects of cervical impairment after the treatment period. These improvements persisted to the 6-month follow-up, but were not observed in the usual care group at any point. These observations together with previous reports indicate that manual therapists should look for features of TMD when examining patients with headache, particularly if treatment fails when directed to the cervical spine. Copyright © 2013. Published by Elsevier Ltd.

Effect of Adding Interferential Current in an Exercise and Manual Therapy Program for Patients With Unilateral Shoulder Impingement Syndrome: A Randomized Clinical Trial.

PubMed

Gomes, Cid André Fidelis de Paula; Dibai-Filho, Almir Vieira; Moreira, William Arruda; Rivas, Shirley Quispe; Silva, Emanuela Dos Santos; Garrido, Ana Claudia Bogik

The purpose of this study was to measure the additional effect of adding interferential current (IFC) to an exercise and manual therapy program for patients with unilateral shoulder impingement syndrome. Forty-five participants were randomly assigned to group 1 (exercise and manual therapy), group 2 (exercise and manual therapy + IFC), or group 3 (exercise and manual therapy + placebo ultrasound). Individuals participated in 16 treatment sessions, twice a week for 8 weeks. The primary outcome of the study was total score of the Shoulder Pain and Disability Index (SPADI). The secondary outcomes were the pain and disability subscales of SPADI, Numeric Rating Scale, and Pain-Related Self-Statement Scale. Adjusted between-group mean differences (MDs) and 95% confidence intervals (CIs) were calculated using linear mixed models. After 16 treatment sessions, statistically significant but not clinically important differences were identified in favor of the exercise and manual therapy program alone in the SPADI-total (group 1 vs group 2, MD 11.12 points, 95% CI 5.90-16.35; group 1 vs group 3, MD 13.43 points, 95% CI 8.21-18.65). Similar results were identified for secondary outcomes. The addition of IFC does not generate greater clinical effects in an exercise and manual therapy program for individuals with unilateral shoulder impingement syndrome. Copyright © 2018. Published by Elsevier Inc.

The comparison of manual lymph drainage and ultrasound therapy on the leg swelling caused by wearing high heels.

PubMed

Lee, Dong-Yeop; Han, Ji-Su; Jang, Eun-Ji; Seo, Dong-Kwon; Hong, Ji-Heon; Lee, Sang-Sook; Lee, Dong-Geol; Yu Lee, Jae-Ho

2014-01-01

One of the major symptoms when women are wearing high heels for a long time is leg swelling. The purpose of this study was to compare the effect of manual lymph drainage with ultrasound therapy. The forty-five healthy women of twenties were participated in this study and divided randomly into three groups; manual lymph drainage group (n=15), ultrasound therapy group (n=15) and control group (n=15). Swelling was measured before wearing the high heels (10 cm-height), after one-hour of wearing the high heels, wearing the high heels of one-hour after the intervention of 15 minutes. Also swelling was calculated by using a tape measure, volumeter and body composition analyzer. Statistical analysis of the comparison between the three groups was performed by one-way ANOVA. Also comparison to the mean value in swelling according to the time was performed by repeated measure ANOVA. As the result of this study, a significant changes have emerged within each of manual lymph drainage, ultrasound therapy and control group (p< 0.05). However, there were no significant differences between each group (p> 0.05). But the mean value of manual lymph drainage group showed the tendency of fast recovering before causing swelling. Therefore, we consider that the clinical treatment of manual lymph drainage and ongoing studies will be made since manual lymph drainage is very effective in releasing the leg swelling caused by wearing high heels and standing for a long time at work.

Targeted Nanoparticles for Kidney Cancer Therapy

DTIC Science & Technology

2013-10-01

AD_________________ Award Number: W81XWH-10-1-0434 TITLE: Targeted Nanoparticles for Kidney Cancer Therapy PRINCIPAL...Targeted Nanoparticles for Kidney Cancer Therapy 5b. GRANT NUMBER W81XWH-10-1-0434 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...lines following treatment with D5 nanotubes. Tthermoablation will be studied initially. Human kidney cancer cells will be injected into the kidney

Targeted nanosystems: Advances in targeted dendrimers for cancer therapy.

PubMed

Yang, Hu

2016-02-01

Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. Much basic and clinical research has been done since the invention of dendrimers, which are highly branched nano-sized molecules with the ability to act as carriers in nanomedicine. In this concise review article, the authors highlighted the current use of dendrimers in immunotherapies and hormone therapies in the fight against cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of visual context in manual target localization

NASA Technical Reports Server (NTRS)

Barry, Susan R.

1993-01-01

During space flight and immediately after return to the 1-g environment of earth, astronauts experience perceptual and sensory-motor disturbances. These changes result from adaptation of the astronaut to the microgravity environment of space. During space flight, sensory information from the eyes, limbs, and vestibular organs is reinterpreted by the central nervous system in order to produce appropriate body movements in the microgravity. This adaptation takes several days to develop. Upon return to earth, the changes in the sensory-motor system are no longer appropriate to a 1-g environment. Over several days, the astronaut must re-adapt to the terrestrial environment. Alterations in sensory-motor function may affect eye-head-hand coordination and, thus, the crewmember's ability to manually locate objects in extrapersonal space. Previous reports have demonstrated that crewmembers have difficulty in estimating joint and limb position and in pointing to memorized target positions on orbit and immediately postflight. The ability to point at or reach toward an object or perform other manual tasks is essential for safe Shuttle operation and may be compromised particularly during re-entry and landing sequences and during possible emergency egress from the Shuttle. An understanding of eye-head-hand coordination and the changes produced during space flight is necessary to develop effective countermeasures. This summer's project formed part of the study of the sensory cues use in the manual localization of objects.

Strategies to overcome size and mechanical disadvantages in manual therapy

PubMed Central

Hazle, Charles R.; Lee, Matthew

2016-01-01

The practice of manual therapy (MT) is often difficult when providing care for large patients and for practitioners small in stature or with other physical limitations. Many MT techniques can be modified using simple principles to require less exertion, permitting consistency with standards of practice even in the presence of physical challenges. Commonly used MT techniques are herein described and demonstrated with alternative preparatory and movement methods, which can also be adopted for use in other techniques. These alternative techniques and the procedures used to adapt them warrant discussion among practitioners and educators in order to implement care, consistent with the best treatment evidence for many common musculoskeletal (MSK) conditions. The inclusion in educational curricula and MT training programs is recommended to enrich skill development in physical therapists (PTs), spanning entry-level practitioners to those pursuing advanced manual skills. PMID:27559282

Attenuation of postoperative adhesions using a modeled manual therapy.

PubMed

Bove, Geoffrey M; Chapelle, Susan L; Hanlon, Katherine E; Diamond, Michael P; Mokler, David J

2017-01-01

Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

Novel targets for HIV therapy.

PubMed

Greene, Warner C; Debyser, Zeger; Ikeda, Yasuhiro; Freed, Eric O; Stephens, Edward; Yonemoto, Wes; Buckheit, Robert W; Esté, José A; Cihlar, Tomas

2008-12-01

There are currently 25 drugs belonging to 6 different inhibitor classes approved for the treatment of human immunodeficiency virus (HIV) infection. However, new anti-HIV agents are still needed to confront the emergence of drug resistance and various adverse effects associated with long-term use of antiretroviral therapy. The 21st International Conference on Antiviral Research, held in April 2008 in Montreal, Canada, therefore featured a special session focused on novel targets for HIV therapy. The session included presentations by world-renowned experts in HIV virology and covered a diverse array of potential targets for the development of new classes of HIV therapies. This review contains concise summaries of discussed topics that included Vif-APOBEC3G, LEDGF/p75, TRIM 5alpha, virus assembly and maturation, and Vpu. The described viral and host factors represent some of the most noted examples of recent scientific breakthroughs that are opening unexplored avenues to novel anti-HIV target discovery and validation, and should feed the antiretroviral drug development pipeline in the near future.

From acute musculoskeletal pain to chronic widespread pain and fibromyalgia: application of pain neurophysiology in manual therapy practice.

PubMed

Nijs, Jo; Van Houdenhove, Boudewijn

2009-02-01

During the past decade, scientific research has provided new insight into the development from an acute, localised musculoskeletal disorder towards chronic widespread pain/fibromyalgia (FM). Chronic widespread pain/FM is characterised by sensitisation of central pain pathways. An in-depth review of basic and clinical research was performed to design a theoretical framework for manual therapy in these patients. It is explained that manual therapy might be able to influence the process of chronicity in three different ways. (I) In order to prevent chronicity in (sub)acute musculoskeletal disorders, it seems crucial to limit the time course of afferent stimulation of peripheral nociceptors. (II) In the case of chronic widespread pain and established sensitisation of central pain pathways, relatively minor injuries/trauma at any locations are likely to sustain the process of central sensitisation and should be treated appropriately with manual therapy accounting for the decreased sensory threshold. Inappropriate pain beliefs should be addressed and exercise interventions should account for the process of central sensitisation. (III) However, manual therapists ignoring the processes involved in the development and maintenance of chronic widespread pain/FM may cause more harm then benefit to the patient by triggering or sustaining central sensitisation.

The Effectiveness and Safety of Manual Therapy on Pain and Disability in Older Persons With Chronic Low Back Pain: A Systematic Review.

PubMed

de Luca, Katie E; Fang, Sheng Hung; Ong, Justin; Shin, Ki-Soo; Woods, Samuel; Tuchin, Peter J

2017-09-01

The aim of this study was to perform a systematic review of the literature of the effectiveness and safety of manual therapy interventions on pain and disability in older persons with chronic low back pain (LBP). A literature search of 4 electronic databases was performed (PubMed, EMBASE, OVID, and CINAHL). Inclusion criteria included randomized controlled trials of manual therapy interventions on older persons who had chronic LBP. Effectiveness was determined by extracting and examining outcomes for pain and disability, with safety determined by the report of adverse events. The PEDro scale was used for quality assessment of eligible studies. The search identified 405 articles, and 38 full-text articles were assessed. Four studies met the inclusion criteria. All trials were of good methodologic quality and had a low risk of bias. The included studies provided moderate evidence supporting the use of manual therapy to reduce pain levels and alleviate disability. A limited number of studies have investigated the effectiveness and safety of manual therapy in the management of older people with chronic LBP. The current evidence to make firm clinical recommendations is limited. Research with appropriately designed trials to investigate the effectiveness and safety of manual therapy interventions in older persons with chronic LBP is required. Copyright © 2017. Published by Elsevier Inc.

Cost-effectiveness of manual therapy for the management of musculoskeletal conditions: a systematic review and narrative synthesis of evidence from randomized controlled trials.

PubMed

Tsertsvadze, Alexander; Clar, Christine; Court, Rachel; Clarke, Aileen; Mistry, Hema; Sutcliffe, Paul

2014-01-01

The purpose of this study was to systematically review trial-based economic evaluations of manual therapy relative to other alternative interventions used for the management of musculoskeletal conditions. A comprehensive literature search was undertaken in major medical, health-related, science and health economic electronic databases. Twenty-five publications were included (11 trial-based economic evaluations). The studies compared cost-effectiveness and/or cost-utility of manual therapy interventions to other treatment alternatives in reducing pain (spinal, shoulder, ankle). Manual therapy techniques (e.g., osteopathic spinal manipulation, physiotherapy manipulation and mobilization techniques, and chiropractic manipulation with or without other treatments) were more cost-effective than usual general practitioner (GP) care alone or with exercise, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. Chiropractic manipulation was found to be less costly and more effective than alternative treatment compared with either physiotherapy or GP care in improving neck pain. Preliminary evidence from this review shows some economic advantage of manual therapy relative to other interventions used for the management of musculoskeletal conditions, indicating that some manual therapy techniques may be more cost-effective than usual GP care, spinal stabilization, GP advice, advice to remain active, or brief pain management for improving low back and shoulder pain/disability. However, at present, there is a paucity of evidence on the cost-effectiveness and/or cost-utility evaluations for manual therapy interventions. Further improvements in the methodological conduct and reporting quality of economic evaluations of manual therapy are warranted in order to facilitate adequate evidence-based decisions among policy makers, health care practitioners, and patients. Copyright © 2014 National University

Gene Therapy and Targeted Toxins for Glioma

PubMed Central

Castro, Maria G.; Candolfi, Marianela; Kroeger, Kurt; King, Gwendalyn D.; Curtin, James F.; Yagiz, Kader; Mineharu, Yohei; Assi, Hikmat; Wibowo, Mia; Muhammad, AKM Ghulam; Foulad, David; Puntel, Mariana; Lowenstein, Pedro R.

2011-01-01

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:21453286

Targeted polymeric nanoparticles for cancer gene therapy

PubMed Central

Kim, Jayoung; Wilson, David R.; Zamboni, Camila G.; Green, Jordan J.

2015-01-01

In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented. PMID:26061296

The control of sequential aiming movements: the influence of practice and manual asymmetries on the one-target advantage.

PubMed

Lavrysen, Ann; Helsen, Werner F; Tremblay, Luc; Elliott, Digby; Adam, Jos J; Feys, Peter; Buekers, Martinus J

2003-04-01

The present experiment was conducted to explore the effect of practice on the one-target advantage in manual aiming, as well as asymmetries in intermanual transfer of training. Reaction and movement times for the first movement were longer in the 2-target than in the 1-target task, regardless of the amount of practice, hand preference and practice hand. When two movements were required, peak velocity was lower and, proportionally, more time was spent after peak velocity. Our kinematic results suggest that the one-target advantage is related to both predefined strategies as well as movement implementation processes during execution. Therefore, an integration of advance planning and on-line explanations for the one-target advantage is suggested. Regarding manual asymmetries, right-handers showed more transfer of training from the left to the right hand than vice versa. Left-handers exhibited a reversed pattern of asymmetric transfer of training to right-handers, but they were more disadvantaged using their non-dominant hand. These latter two findings have implications for models of manual asymmetry and upper limb control.

Heart failure—potential new targets for therapy

PubMed Central

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

Targeted Therapy for Melanoma

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

Quinn, Thomas; Moore, Herbert

The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg 11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg 11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particularmore » note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.« less

The effectiveness and cost-evaluation of manual therapy and physical therapy in patients with sub-acute and chronic non specific neck pain. Rationale and design of a Randomized Controlled Trial (RCT)

PubMed Central

2010-01-01

Background Manual Therapy applied to patients with non specific neck pain has been investigated several times. In the Netherlands, manual therapy as applied according to the Utrecht School of Manual Therapy (MTU) has not been the subject of a randomized controlled trial. MTU differs in diagnoses and treatment from other forms of manual therapy. Methods/Design This is a single blind randomized controlled trial in patients with sub-acute and chronic non specific neck pain. Patients with neck complaints existing for two weeks (minimum) till one year (maximum) will participate in the trial. 180 participants will be recruited in thirteen primary health care centres in the Netherlands. The experimental group will be treated with MTU during a six week period. The control group will be treated with physical therapy (standard care, mainly active exercise therapy), also for a period of six weeks. Primary outcomes are Global Perceived Effect (GPE) and functional status (Neck Disability Index (NDI-DV)). Secondary outcomes are neck pain (Numeric Rating Scale (NRS)), Eurocol, costs and quality of life (SF36). Discussion This paper presents details on the rationale of MTU, design, methods and operational aspects of the trial. Trial registration ClinicalTrials.gov Identifier: NCT00713843 PMID:20096136

Targeted therapies in gastric cancer and future perspectives.

PubMed

Yazici, Ozan; Sendur, M Ali Nahit; Ozdemir, Nuriye; Aksoy, Sercan

2016-01-14

Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.

Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5b. GRANT NUMBER... therapy resistance/sensitivity, identification of new therapeutic targets through high quality genomic analyses, providing access to the highest quality

Stabilization exercise compared to general exercises or manual therapy for the management of low back pain: A systematic review and meta-analysis.

PubMed

Gomes-Neto, Mansueto; Lopes, Jordana Moura; Conceição, Cristiano Sena; Araujo, Anderson; Brasileiro, Alécio; Sousa, Camila; Carvalho, Vitor Oliveira; Arcanjo, Fabio Luciano

2017-01-01

We performed a systematic review with a meta-analysis to examine the efficacy of stabilization exercises versus general exercises or manual therapy in patients with low back pain. We searched MEDLINE, Cochrane Controlled Trials, Scielo, and CINAHL (from the earliest date available to November 2014) for randomized controlled trials that examined the efficacy of stabilization exercises compared to general exercises or manual therapy on pain, disability, and function in patients with low back pain. Weighted mean differences (WMD) and 95% confidence intervals were calculated. Eleven studies met the inclusion criteria (413 stabilization exercises patients, 297 general exercises patients, and 185 manual therapy patients). Stabilization exercises may provide greater benefit than general exercise for pain reduction and improvement in disability. Stabilization exercise improved pain with a WMD of -1.03 (95% CI: -1.29 to -0.27) and improved disability with a WMD of -5.41 (95% CI: -8.34 to -2.49). There were no significant differences in pain and disability scores among participants in the stabilization exercise group compared to those in the manual therapy group. Stabilization exercises were as efficacious as manual therapy in decreasing pain and disability and should be encouraged as part of musculoskeletal rehabilitation for low back pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Will nanotechnology influence targeted cancer therapy?

PubMed Central

Grimm, Jan; Scheinberg, David A.

2011-01-01

The rapid development of techniques that enable synthesis (and manipulation) of matter on the nanometer scale, as well as the development of new nano-materials, will play a large role in disease diagnosis and treatment, specifically in targeted cancer therapy. Targeted nanocarriers are an intriguing means to selectively deliver high concentrations of cytotoxic agents or imaging labels directly to the cancer site. Often solubility issues and an unfavorable biodistribution can result in a suboptimal response of novel agents even though they are very potent. New nanoparticulate formulations allow simultaneous imaging and therapy (“theranostics”), which can provide a realistic means for the clinical implementation of such otherwise suboptimal formulations. In this review we will not attempt to provide a complete overview of the rapidly enlarging field of nanotechnology in cancer; rather, we will present properties specific to nanoparticles, and examples of their uses, which demonstrate their importance for targeted cancer therapy. PMID:21356476

The effect of manual therapy and exercise in patients with chronic low back pain: Double blind randomized controlled trial.

PubMed

Ulger, Ozlem; Demirel, Aynur; Oz, Müzeyyen; Tamer, Seval

2017-11-06

To determine the effects of spinal stabilization exercises (SSE) and manual therapy methods on pain, function and quality of life (QoL) levels in individuals with chronic low back pain (CLBP). A total of one-hundred thirteen patients diagnosed as CLBP were enrolled to the study. The patients allocated into Spinal Stabilization group (SG) and manual therapy group (MG), randomly. While SSE performed in SG, soft tissue mobilizations, muscle-energy techniques, joint mobilizations and manipulations were performed in MG. While the severity of pain was assessed with Visual Analog Scale (VAS), Oswestry Disability Index (ODI) and Short Form 36 (SF-36) assessments were performed to evaluate the functional status and QoL, respectively. All assessments were repeated before and after the treatment. Intragroup analyses both treatments were effective in terms of sub parameters of pain, function and life quality (p< 0.05). Inter group analyses, there was more reduction in pain and improvement in functional status in favor of MG (p< 0.05). This study showed that SSE and manual therapy methods have the same effects on QoL, while the manual treatment is more effective on the pain and functional parameters in particular.

Manual therapy in addition to physiotherapy does not improve clinical or economic outcomes after ankle fracture.

PubMed

Lin, Chung-Wei Christine; Moseley, Anne M; Haas, Marion; Refshauge, Kathryn M; Herbert, Robert D

2008-06-01

The primary aim of this study was to determine the effectiveness and cost-effectiveness of adding manual therapy to a physiotherapy programme for ankle fracture. Assessor-blinded randomized controlled trial. Ninety-four adults were recruited within one week of cast removal for isolated ankle fracture. Inclusion criteria were: they were able to weight-bear as tolerated or partial weight-bear, were referred for physiotherapy, and experienced pain. Ninety-one participants completed the study. Participants were randomly allocated to receive manual therapy (anterior-posterior joint mobilization over the talus) plus a standard physiotherapy programme (experimental), or the standard physiotherapy programme only (control). They were assessed by a blinded assessor at baseline, and at 4, 12 and 24 weeks. The main outcomes were activity limitation and quality of life. Information on costs and healthcare utilization was collected every 4 weeks up to 24 weeks. There were no clinically worthwhile differences in activity limitation or quality of life between groups at any time-point. There was also no between-group difference in quality-adjusted life-years, but the experimental group incurred higher out-of-pocket costs (mean between-group difference = AU$200, 95% confidence interval 26-432). When provided in addition to a physiotherapy programme, manual therapy did not enhance outcome in adults after ankle fracture.

A comparison of home-based exercise programs with and without self-manual therapy in individuals with knee osteoarthritis in community.

PubMed

Cheawthamai, Kornkamon; Vongsirinavarat, Mantana; Hiengkaew, Vimonwan; Saengrueangrob, Sasithorn

2014-07-01

The present study aimed to compare the effectiveness of the treatment programs of home-based exercise with and without self-manual therapy in individuals with knee osteoarthritis (knee OA) in community. Forty-three participants with knee OA were randomly assigned in groups. All participants received the same home-based exercise program with or without self-manual therapy over 12 weeks. Outcome measures were pain intensity, range of motions, six-minute walk test distance, the knee injury and osteoarthritis outcome score (KOOS), short-form 36 (SF-36) and satisfaction. The results showed that the self-manual therapy program significantly decreased pain at 4 weeks, increased flexion and extension at 4 and 12 weeks, and improved the KOOS in pain item and SF-36 in physical function and mental health items. The home-based exercise group showed significant increase of the six-minute walk distance at 4 and 12 weeks, improvements in the KOOS in pain and symptom items and SF-36 in the physical function and role-emotional items. Overall, the results favored a combination of self-manual therapy and home-based exercise for patients with knee OA, which apparently showed superior benefits in decreasing pain and improving active knee range of motions.

Increasing Orgasm and Decreasing Dyspareunia by a Manual Physical Therapy Technique

PubMed Central

Wurn, Lawrence J; Wurn, Belinda F; Roscow, Amanda S; King, C Richard; Scharf, Eugenia S; Shuster, Jonathan J

2004-01-01

Context Female sexual pain and dysfunction Objective To evaluate the effectiveness of a new site-specific, manual soft-tissue therapy in increasing orgasm and reducing dyspareunia (painful intercourse) in women with histories indicating abdominopelvic adhesion formation. Design and Intervention A total of 29 new patients presenting with infertility or abdominopelvic pain-related problems, and also indicating sexual pain or dysfunction, received a series of treatments (mean, 19.5 hours) designed to address biomechanical dysfunction and restricted mobility due to adhesions affecting the reproductive organs and adjacent structures. Outcome Measures Primary outcome measures were post-test vs pretest scores on: (1) the Female Sexual Function Index (FSFI) full scale, orgasm domain, and pain domain; and (2) 3 supplemental 10-point rating scales of sexual pain levels. Secondary outcome measures were post-test vs pretest scores in the other 4 FSFI domains (desire, arousal, lubrication, and satisfaction). The Wilcoxon signed-rank test was used for all statistical analyses. Results For the 23 patients available for follow-up, the paired FSFI post-test vs pretest scores were significant (P ≤ .003) on all measures. Of the 17 patients who completed the 3 sexual pain scales, the paired post-test vs pretest scores were significant (P ≤ .002) Conclusions Many cases of inhibited orgasm, dyspareunia, and other aspects of sexual dysfunction seem to be treatable by a distinctive, noninvasive manual therapy with no risks and few, if any, adverse effects. The therapy should be considered a new adjunct to existing gynecologic and medical treatments. PMID:15775874

Changes in co-contraction during stair descent after manual therapy protocol in knee osteoarthritis: A pilot, single-blind, randomized study.

PubMed

Cruz-Montecinos, Carlos; Flores-Cartes, Rodrigo; Montt-Rodriguez, Agustín; Pozo, Esteban; Besoaín-Saldaña, Alvaro; Horment-Lara, Giselle

2016-10-01

Manual therapy has shown clinical results in patients with knee osteoarthritis. However, the biomechanical aspects during functional tasks have not been explored in depth. Through surface electromyography, the medial and lateral co-contractions of the knee were measured while descending stairs, prior and posterior to applying a manual therapy protocol in the knee, with emphasis on techniques of joint mobilization and soft-tissue management. Sixteen females with slight or moderate knee osteoarthritis were recruited (eight experimental, eight control). It was observed that the lateral co-contraction index of the experimental group, posterior to intervention, increased by 11.7% (p = 0.014). The application of a manual therapy protocol with emphasis on techniques of joint mobilization and soft-tissue management modified lateral co-contraction, which would have a protective effect on the joint. Copyright © 2016 Elsevier Ltd. All rights reserved.

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee. 2: economic evaluation alongside a randomized controlled trial.

PubMed

Pinto, D; Robertson, M C; Abbott, J H; Hansen, P; Campbell, A J

2013-10-01

To evaluate the cost effectiveness of manual physiotherapy, exercise physiotherapy, and a combination of these therapies for patients with osteoarthritis of the hip or knee. 206 Adults who met the American College of Rheumatology criteria for hip or knee osteoarthritis were included in an economic evaluation from the perspectives of the New Zealand health system and society alongside a randomized controlled trial. Resource use was collected using the Osteoarthritis Costs and Consequences Questionnaire. Quality-adjusted life years (QALYs) were calculated using the Short Form 6D. Willingness-to-pay threshold values were based on one to three times New Zealand's gross domestic product (GDP) per capita of NZ$ 29,149 (in 2009). All three treatment programmes resulted in incremental QALY gains relative to usual care. From the perspective of the New Zealand health system, exercise therapy was the only treatment to result in an incremental cost utility ratio under one time GDP per capita at NZ$ 26,400 (-$34,081 to $103,899). From the societal perspective manual therapy was cost saving relative to usual care for most scenarios studied. Exercise therapy resulted in incremental cost utility ratios regarded as cost effective but was not cost saving. For most scenarios combined therapy was not as cost effective as the two therapies alone. In this study, exercise therapy and manual therapy were more cost effective than usual care at policy relevant values of willingness-to-pay from both the perspective of the health system and society. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12608000130369. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Development of iPad application "Postima" for quantitative analysis of the effects of manual therapy

NASA Astrophysics Data System (ADS)

Sugiyama, Naruhisa; Shirakawa, Tomohiro

2017-07-01

The technical difficulty of diagnosing joint misalignment and/or dysfunction by quantitative evaluation is commonly acknowledged among manual therapists. Usually, manual therapists make a diagnosis based on a combination of observing patient symptoms and performing physical examinations, both of which rely on subjective criteria and thus contain some uncertainty. We thus sought to investigate the correlations among posture, skeletal misalignment, and pain severity over the course of manual therapy treatment, and to explore the possibility of establishing objective criteria for diagnosis. For this purpose, we developed an iPad application that realizes the measurement of patients' postures and analyzes them quantitatively. We also discuss the results and effectiveness of the measurement and analysis.

Boron neutron capture therapy: Moving toward targeted cancer therapy.

PubMed

Mirzaei, Hamid Reza; Sahebkar, Amirhossein; Salehi, Rasoul; Nahand, Javid Sadri; Karimi, Ehsan; Jaafari, Mahmoud Reza; Mirzaei, Hamed

2016-01-01

Boron neutron capture therapy (BNCT) occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

PNF and manual therapy treatment results of patients with cervical spine osteoarthritis.

PubMed

Maicki, Tomasz; Bilski, Jan; Szczygieł, Elżbieta; Trąbka, Rafał

2017-09-22

The aim of this study was to evaluate the effectiveness of PNF and manual therapy methods in the treatment of patients with cervical spine osteoarthritis, especially their efficacy in reducing pain and improving functionality in everyday life. Long-term results were also compared in order to determine which method of treatment is more effective. Eighty randomly selected females aged 45-65 were included in the study. They were randomly divided into two groups of 40 persons. One group received PNF treatment and the other received manual therapy (MAN.T). To evaluate functional capabilities, the Functional Rating Index was used. To evaluate changes in pain, a shortened version of the McGill Questionnaire was used. The PNF group achieved a greater reduction in pain than the MAN.T group. The PNF group showed a greater improvement in performing daily activities such as sleeping, personal care, travelling, work, recreation, lifting, walking and standing as well as decreased intensity and frequency of pain compared to the MAN.T group. The PNF method proved to be more effective in both short (after two weeks) and long (after three months) term.

The Effects of Manual Therapy Using Joint Mobilization and Flexion-distraction Techniques on Chronic Low Back Pain and Disc Heights

PubMed Central

Choi, Jioun; Hwangbo, Gak; Park, Jungseo; Lee, Sangyong

2014-01-01

[Purpose] The purpose of this study was to examine the effects of manual therapy using joint mobilization and flexion-distraction techniques on chronic low back pain and disc heights. [Subjects] This study was conducted with 31 chronic low back pain patients who were divided into a manual therapy group (MTG; n=16) and a spinal decompression therapy group (SDTG; n=15). [Methods] The MTG was treated using joint mobilization techniques and flexion-distraction techniques, and the SDTG was treated using spinal decompression therapeutic apparatuses. Conservative physical therapy was used in both groups, and the therapy was implemented three times per week for 6 weeks. The visual analog scale (VAS) was used to measure patient’s low back pain scores, and a picture archiving and communication system was used to measure disc height by comparing and analyzing the images. [Results] In comparisons of the VAS within each of the two groups, both the MTG and the SDTG showed significant decreases. In comparisons of disc height within each of the two groups, the MTG showed statistically significant increases. [Conclusion] Manual therapy using joint mobilization techniques and flexion-distraction techniques is considered an effective intervention for addressing low back pain and disc heights in patients with chronic low back pain. PMID:25202191

International framework for examination of the cervical region for potential of Cervical Arterial Dysfunction prior to Orthopaedic Manual Therapy intervention.

PubMed

Rushton, A; Rivett, D; Carlesso, L; Flynn, T; Hing, W; Kerry, R

2014-06-01

A consensus clinical reasoning framework for best practice for the examination of the cervical spine region has been developed through an iterative consultative process with experts and manual physical therapy organisations. The framework was approved by the 22 member countries of the International Federation of Orthopaedic Manipulative Physical Therapists (October 2012). The purpose of the framework is to provide guidance to clinicians for the assessment of the cervical region for potential of Cervical Arterial Dysfunction in advance of planned management (inclusive of manual therapy and exercise interventions). The best, most recent scientific evidence is combined with international expert opinion, and is presented with the intention to be informative, but not prescriptive; and therefore as an aid to the clinician's clinical reasoning. Important underlying principles of the framework are that 1] although presentations and adverse events of Cervical Arterial Dysfunction are rare, it is a potentially serious condition and needs to be considered in musculoskeletal assessment; 2] manual therapists cannot rely on the results of one clinical test to draw conclusions as to the presence or risk of Cervical Arterial Dysfunction; and 3] a clinically reasoned understanding of the patient's presentation, including a risk:benefit analysis, following an informed, planned and individualised assessment, is essential for recognition of this condition and for safe manual therapy practice in the cervical region. Clinicians should also be cognisant of jurisdictionally specific requirements and obligations, particularly related to patient informed consent, when intending to use manual therapy in the cervical region. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical presentation and manual therapy for upper quadrant musculoskeletal conditions

PubMed Central

Isabel de-la-Llave-Rincón, Ana; Puentedura, Emilio J; Fernández-de-las-Peñas, César

2011-01-01

In recent years, increased knowledge of the pathogenesis of upper quadrant pain syndromes has translated to better management strategies. Recent studies have demonstrated evidence of peripheral and central sensitization mechanisms in different local pain syndromes of the upper quadrant such as idiopathic neck pain, lateral epicondylalgia, whiplash-associated disorders, shoulder impingement, and carpal tunnel syndrome. Therefore, a treatment-based classification approach where subjects receive matched interventions has been developed and, it has been found that these patients experience better outcomes than those receiving non-matched interventions. There is evidence suggesting that the cervical and thoracic spine is involved in upper quadrant pain. Spinal manipulation has been found to be effective for patients with elbow pain, neck pain, or cervicobrachial pain. Additionally, it is known that spinal manipulative therapy exerts neurophysiological effects that can activate pain modulation mechanisms. This paper exposes some manual therapies for upper quadrant pain syndromes, based on a nociceptive pain rationale for modulating central nervous system including trigger point therapy, dry needling, mobilization or manipulation, and cognitive pain approaches. PMID:23115473

Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

PubMed Central

Sun, Hongguang; Zhu, Xun; Lu, Patrick Y; Rosato, Roberto R; Tan, Wen; Zu, Youli

2014-01-01

Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy. PMID:25093706

Apatinib as targeted therapy for sarcoma

PubMed Central

Li, Feng; Liao, Zhichao; Zhang, Chao; Zhao, Jun; Xing, Ruwei; Teng, Sheng; Zhang, Jin; Yang, Yun; Yang, Jilong

2018-01-01

Sarcomas are a group of malignant tumors originating from mesenchymal tissue with a variety of cell subtypes. Despite several major treatment breakthroughs, standard treatment using surgery, radiation, and chemotherapy has failed to improve overall survival. Therefore, there is an urgent need to explore new strategies and innovative therapies to further improve the survival rates of patients with sarcomas. Pathological angiogenesis has an important role in the growth and metastasis of tumors. Vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) play a central role in tumor angiogenesis and represent potential targets for anticancer therapy. As a novel targeted therapy, especially with regard to angiogenesis, apatinib is a new type of small molecule tyrosine kinase inhibitor that selectively targets VEGFR-2 and has shown encouraging anticancer activity in a wide range of malignancies, including gastric cancer, non-small cell lung cancer, breast cancer, hepatocellular carcinoma, and sarcomas. In this review, we summarize the preclinical and clinical data for apatinib, focusing primarily on its use in the treatment of sarcomas. PMID:29849960

Chemoresistance and targeted therapies in ovarian and endometrial cancers

PubMed Central

Brasseur, Kevin; Gévry, Nicolas; Asselin, Eric

2017-01-01

Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this acquired chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways (PI3K/AKT, MAPK, EGFR, mTOR, estrogen signaling) and tumor suppressors (P53 and Par-4). To overcome these resistances, a new type of therapy has emerged named targeted therapy. The principle of targeted therapy is simple, taking advantage of changes acquired in malignant cancer cells (receptors, proteins, mechanisms) by using compounds specifically targeting these, thus limiting their action on healthy cells. Targeted therapies are emerging and many clinical trials targeting these pathways, frequently involved in chemoresistance, have been tested on gynecological cancers. Despite some targets being less efficient than expected as mono-therapies, the combination of compounds seems to be the promising avenue. For instance, we demonstrate using ChIP-seq analysis that estrogen downregulate tumor suppressor Par-4 in hormone-dependent cells by directly binding to its DNA regulatory elements and inhibiting estrogen signaling could reinstate Par-4 apoptosis-inducing abilities. This review will focus on the chemoresistance mechanisms and the clinical trials of targeted therapies associated with these, specifically for endometrial and ovarian cancers. PMID:28008141

EGFR-targeted therapies in the post-genomic era.

PubMed

Xu, Mary Jue; Johnson, Daniel E; Grandis, Jennifer R

2017-09-01

Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials. The humanized monoclonal antibody nimotuzumab is also approved for head and neck cancers in Cuba, Argentina, Colombia, Peru, India, Ukraine, Ivory Coast, and Gabon in addition to nasopharyngeal cancers in China. Few other EGFR-targeted therapeutics for head and neck cancers have led to as significant responses as seen in lung carcinomas, for instance. Recent genome sequencing of head and neck tumors has helped identify patient subgroups with improved response to EGFR inhibitors, for example, cetuximab in patients with the KRAS-variant and the tyrosine kinase inhibitor erlotinib for tumors harboring MAPK1 E322K mutations. Genome sequencing has furthermore broadened our understanding of dysregulated pathways, holding the potential to enhance the benefit derived from therapies targeting EGFR.

Efficacy of complete decongestive therapy and manual lymphatic drainage on treatment-related lymphedema in breast cancer

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

Koul, Rashmi; Dufan, Tarek; Russell, Catherine

2007-03-01

Objective: To evaluate the results of combined decongestive therapy and manual lymphatic drainage in patients with breast cancer-related lymphedema. Methods and Materials: The data from 250 patients were reviewed. The pre- and posttreatment volumetric measurements were compared, and the correlation with age, body mass index, and type of surgery, chemotherapy, and radiotherapy was determined. The Spearman correlation coefficients and Wilcoxon two-sample test were used for statistical analysis. Results: Of the 250 patients, 138 were included in the final analysis. The mean age at presentation was 54.3 years. Patients were stratified on the basis of the treatment modality used for breastmore » cancer management. Lymphedema was managed with combined decongestive therapy in 55%, manual lymphatic drainage alone in 32%, and the home program in 13%. The mean pretreatment volume of the affected and normal arms was 2929 and 2531 mL. At the end of 1 year, the posttreatment volume of the affected arm was 2741 mL. The absolute volume of the affected arm was reduced by a mean of 188 mL (p < 0.0001). The type of surgery (p = 0.0142), age (p = 0.0354), and body mass index (p < 0.0001) were related to the severity of lymphedema. Conclusion: Combined decongestive therapy and manual lymphatic drainage with exercises were associated with a significant reduction in the lymphedema volume.« less

Novel Targeted Therapies for Inflammatory Breast Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0461 TITLE: Novel Targeted Therapies for Inflammatory Breast Cancer PRINCIPAL INVESTIGATOR: Jose Silva CONTRACTING...CONTRACT NUMBER Novel Targeted Therapies for Inflammatory Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0461 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) l 5d...NOTES 14. ABSTRACT Inflammatory breast cancer (IBC, ~5% of all breast cancers ) is the most lethal form of breast cancer , presenting a 5- year

An online community of practice to support evidence-based physiotherapy practice in manual therapy.

PubMed

Evans, Cathy; Yeung, Euson; Markoulakis, Roula; Guilcher, Sara

2014-01-01

The purpose of this study was to explore how a community of practice promoted the creation and sharing of new knowledge in evidence-based manual therapy using Wenger's constructs of mutual engagement, joint enterprise, and shared repertoire as a theoretical framework. We used a qualitative approach to analyze the discussion board contributions of the 19 physiotherapists who participated in the 10-week online continuing education course in evidence-based practice (EBP) in manual therapy. The course was founded on community of practice, constructivism, social, and situated learning principles. The 1436 postings on 9 active discussion boards revealed that the community of practice was a social learning environment that supported strong participation and mutual engagement. Design features such as consistent facilitation, weekly guiding questions, and collaborative assignments promoted the creation and sharing of knowledge. Participants applied research evidence to the contexts in which they worked through reflective comparison of what they were reading to its applicability in their everyday practice. Participants' shared goals contributed to the common ground established in developing collective knowledge about different study designs, how to answer research questions, and the difficulties of conducting sound research. An online longitudinal community of practice utilized as a continuing education approach to deliver an online course based on constructivist and social learning principles allowed geographically dispersed physiotherapists to be mutually engaged in a joint enterprise in evidence-based manual therapy. Advantages included opportunity for reflection, modeling, and collaboration. Future studies should examine the impact of participation on clinical practice. © 2014 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on Continuing Medical Education, Association for Hospital

Energy costs of manual therapy: effects of plinth height and an assistive device.

PubMed

O'Connell, D G; Holmes, C F; Santos, J L; Jordan, E; Acosta, F

1994-01-01

The purpose of this investigation was to examine the metabolic and cardiopulmonary responses of an experienced therapist (8 years experience) performing manual therapy at standard (S) plinth height (31 in), elevated (E) plinth height (38 in), and standard (SMTH) and elevated (EMTH) plinth height wearing a manual therapy harness (MTH). The MTH, developed by one of the investigators (J.L.S.), is a vestlike device worn by the therapist, which, when attached to the patient, can be used to distract articular surfaces. The MTH allows the therapist more freedom of hand movement and use of body weight to help provide joint distraction. Inferior glide (Grade 3-Maitland) was provided to the lift hip of 12 individuals at a rate of 20 oscillations per minute for 4 minutes, continuously, so that steady-rate metabolic conditions could be established. Mean body mass and height for the 12 individuals was 70±10.5 kg and 174.5±13 cm, respectively. The therapist's heart rate returned to resting levels between each of the randomly assigned treatments. One subject was treated daily. The therapist (age 32) was chosen because of his clinical experience, similar height (172 em) and weight (73 kg) to the average adult American male, and excellent intra- and interday (5%≤ METs, 5%≤ HR) reproducibility. Metabolic equivalents (METs), heart rate (HR), and rate of perceived exertion (RPE) were measured and averaged for the last 2 minutes of each treatment condition. The therapist was unaware of day-to-day test results except for RPE. Mean METs were 3. 7,3.2,2.6, and 2.4 for S, E, SMTH, and EMTH, respectively. Mean HRs were .117, 110, 104, and 93 beats/min for S, E, SMTH, and EMTH, respectively. RPE was 11. 0,8.7, 7.9, and 7.3jorS, E, SMTH, and EMTH, respectively. Repeated-measures analysis of variance (Scheffé F-test) revealed that SMTH and EMTH METs were similar, and significantly different (p≤0.05) from Sand E. METs for E were significantly different and lower than for S. HRs were

Targeted therapies for the treatment of leukemia.

PubMed

Stull, Dawn Marie

2003-05-01

To review novel targeted therapies for the treatment of leukemia. Professional journals, books, and government publications. Nonspecific cytotoxic chemotherapeutic agents provide marginal therapeutic benefit and significant toxicity when used in the treatment of leukemia. There is a tremendous need for new therapies with increased efficacy and decreased adverse effects. Advances in molecular science, genetics, and immunology, along with improved laboratory technology, have led to the discovery of unique targets integral to the growth and proliferation of malignant cells which are providing the foundation for the development of a new generation of antitumor agents. Nurses must be prepared to educate patients, administer novel therapies, and manage side effects.

Manual therapy as an effective treatment for fibrosis in a rat model of upper extremity overuse injury

PubMed Central

Bove, Geoffrey M.; Harris, Michele Y; Zhao, Huaqing; Barbe, Mary F.

2016-01-01

Key clinical features of carpal tunnel syndrome and other types of cumulative trauma disorders of the hand and wrist include pain and functional disabilities. Mechanistic details remain under investigation but may involve tissue inflammation and/or fibrosis. We examined the effectiveness of modeled manual therapy (MMT) as a treatment for sensorimotor behavior declines and increased fibrogenic processes occurring in forearm tissues of rats performing an high repetition high force (HRHF) reaching and grasping task for 12 weeks. Young adult, female rats were examined: food restricted control rats (FRC, n=12); rats that were trained for 6 weeks before performing the HRHF task for 12 weeks with no treatment (HRHF-CON, n=11); and HRHF task rats received modeled manual therapy (HRHF-MMT, n=5) for 5 days/week for the duration of the 12-week of task. Rats receiving the MMT expressed fewer discomfort-related behaviors, and performed progressively better in the HRHF task. Grip strength, while decreased after training, improved following MMT. Fibrotic nerve and connective tissue changes (increased collagen and TGF-β1 deposition) present in 12-week HRHF-CON rats were significantly decreased in 12-week HRHF-MMT rats. These observations support the investigation of manual therapy as a preventative for repetitive motion disorders. PMID:26810536

Changing strategies for target therapy in gastric cancer.

PubMed

Lee, Suk-Young; Oh, Sang Cheul

2016-01-21

In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

A combined treatment approach emphasizing impairment-based manual physical therapy for plantar heel pain: a case series.

PubMed

Young, Brian; Walker, Michael J; Strunce, Joseph; Boyles, Robert

2004-11-01

Case series. To describe an impairment-based physical therapy treatment approach for 4 patients with plantar heel pain. There is limited evidence from clinical trials on which to base treatment decision making for plantar heel pain. Four patients completed a course of physical therapy based on an impairment-based model. All patients received manual physical therapy and stretching. Two patients were also treated with custom orthoses, and 1 patient received an additional strengthening program. Outcome measures included a numeric pain rating scale (NPRS) and self-reported functional status. Symptom duration ranged from 6 to 52 weeks (mean duration+/-SD, 33+/-19 weeks). Treatment duration ranged from 8 to 49 days (mean duration+/-SD, 23+/-18 days), with number of treatment sessions ranging from 2 to 7 (mode, 3). All 4 patients reported a decrease in NPRS scores from an average (+/-SD) of 5.8+/-2.2 to 0 (out of 10) during previously painful activities. Additionally, all patients returned to prior activity levels. In this case series, patients with plantar heel pain treated with an impairment-based physical therapy approach emphasizing manual therapy demonstrated complete pain relief and full return to activities. Further research is necessary to determine the effectiveness of impairment-based physical therapy interventions for patients with plantar heel pain/plantar fasciitis.

Adverse effects as a consequence of being the subject of orthopaedic manual therapy training, a worldwide retrospective survey.

PubMed

Thoomes-de Graaf, M; Thoomes, E; Carlesso, L; Kerry, R; Rushton, A

2017-06-01

Physical therapists (PTs) use a range of manual therapy techniques developed to an advanced level through postgraduate orthopaedic manipulative physical therapy (OMPT) programmes. The aim of this study was to describe the adverse effects experienced by students after having techniques performed on them as part of their OMPT training. A descriptive online survey of current students and recent graduates (≤5 years)m of OMPT programmes across the 22 Member Organisations of the International Federation of Orthopaedic Manipulative Physical Therapists. The questionnaire was completed by 1640 respondents across 22 countries (1263 graduates, 377 students. Some 60% of respondents reported never having experienced adverse effects during their manual therapy training. Of the 40% who did, 66.4% reported neck pain, 50.9% headache and 32% low back pain. Most reports of neck pain started after a manipulation and/or mobilisation, of which 53.4% lasted ≤24 h, 38.1% > 24 h but <3 months and 13.7% still experienced neck pain to date. A small percentage of respondents (3.3%) reported knowing of a fellow student experiencing a major adverse effect. Mild to moderate adverse effects after practising manual therapy techniques are commonly reported, but usually resolve within 24 h. However, this survey has identified the reported occurrence of major adverse effects that warrant further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Manual therapy in the management of a patient with a symptomatic Morton's Neuroma: A case report.

PubMed

Sault, Josiah D; Morris, Matthew V; Jayaseelan, Dhinu J; Emerson-Kavchak, Alicia J

2016-02-01

Patients with Morton's neuroma are rarely referred to physical therapy. This case reports the resolution of pain, increase in local pressure pain thresholds, and improvement of scores on the Lower Extremity Functional Scale and Foot and Ankle Ability Measure following a course of joint based manual therapy for a patient who had failed standard conservative medical treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Additional Effect of Static Ultrasound and Diadynamic Currents on Myofascial Trigger Points in a Manual Therapy Program for Patients With Chronic Neck Pain: A Randomized Clinical Trial.

PubMed

Dibai-Filho, Almir Vieira; de Oliveira, Alessandra Kelly; Girasol, Carlos Eduardo; Dias, Fabiana Rodrigues Cancio; Guirro, Rinaldo Roberto de Jesus

2017-04-01

To assess the additional effect of static ultrasound and diadynamic currents on myofascial trigger points in a manual therapy program to treat individuals with chronic neck pain. A single-blind randomized trial was conducted. Both men and women, between ages 18 and 45, with chronic neck pain and active myofascial trigger points in the upper trapezius were included in the study. Subjects were assigned to 3 different groups: group 1 (n = 20) was treated with manual therapy; group 2 (n = 20) was treated with manual therapy and static ultrasound; group 3 (n = 20) was treated with manual therapy and diadynamic currents. Individuals were assessed before the first treatment session, 48 hours after the first treatment session, 48 hours after the tenth treatment session, and 4 weeks after the last session. There was no group-versus-time interaction for Numeric Rating Scale, Neck Disability Index, Pain-Related Self-Statement Scale, pressure pain threshold, cervical range of motion, and skin temperature (F-value range, 0.089-1.961; P-value range, 0.106-0.977). Moreover, we found no differences between groups regarding electromyographic activity (P > 0.05). The use of static ultrasound or diadynamic currents on myofascial trigger points in upper trapezius associated with a manual therapy program did not generate greater benefits than manual therapy alone.

Knee extension and stiffness in osteoarthritic and normal knees: a videofluoroscopic analysis of the effect of a single session of manual therapy.

PubMed

Taylor, Alden L; Wilken, Jason M; Deyle, Gail D; Gill, Norman W

2014-04-01

Descriptive biomechanical study using an experimental repeated-measures design. To quantify the response of participants with and without knee osteoarthritis (OA) to a single session of manual physical therapy. The intervention consisted primarily of joint mobilization techniques, supplemented by exercises, aiming to improve knee extension. While manual therapy benefits patients with knee OA, there is limited research quantifying the effects of a manual therapy treatment session on either motion or stiffness of osteoarthritic and normal knees. Methods The study included 5 participants with knee OA and 5 age-, gender-, and body mass index-matched healthy volunteers. Knee extension motion and stiffness were measured with videofluoroscopy before and after a 30-minute manual therapy treatment session. Analysis of variance and intraclass correlation coefficients were used to analyze the data. Participants with knee OA had restricted knee extension range of motion at baseline, in contrast to the participants with normal knees, who had full knee extension. After the therapy session, there was a significant increase in knee motion in participants with knee OA (P = .004) but not in those with normal knees (P = .201). For stiffness data, there was no main effect for time (P = .903) or load (P = .274), but there was a main effect of group (P = .012), with the participants with healthy knees having greater stiffness than those with knee OA. Reliability, using intraclass correlation coefficient model 3,3, for knee angle measurements between imaging sessions for all loading conditions was 0.99. Reliability (intraclass correlation coefficient model 3,1) for intraimage measurements was 0.97. End-range knee extension stiffness was greater in the participants with normal knees than those with knee OA. The combination of lesser stiffness and lack of motion in those with knee OA, which may indicate the potential for improvement, may explain why increased knee extension angle was

Targeted cancer therapy--are the days of systemic chemotherapy numbered?

PubMed

Joo, Won Duk; Visintin, Irene; Mor, Gil

2013-12-01

Targeted therapy or molecular targeted therapy has been defined as a type of treatment that blocks the growth of cancer cells by interfering with specific cell molecules required for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells as with traditional chemotherapy. There is a growing number of FDA approved monoclonal antibodies and small molecules targeting specific types of cancer suggestive of the growing relevance of this therapeutic approach. Targeted cancer therapies, also referred to as "Personalized Medicine", are being studied for use alone, in combination with other targeted therapies, and in combination with chemotherapy. The objective of personalized medicine is the identification of patients that would benefit from a specific treatment based on the expression of molecular markers. Examples of this approach include bevacizumab and olaparib, which have been designated as promising targeted therapies for ovarian cancer. Combinations of trastuzumab with pertuzumab, or T-DM1 and mTOR inhibitors added to an aromatase inhibitor are new therapeutic strategies for breast cancer. Although this approach has been seen as a major step in the expansion of personalized medicine, it has substantial limitations including its high cost and the presence of serious adverse effects. The Cancer Genome Atlas is a useful resource to identify novel and more effective targets, which may help to overcome the present limitations. In this review we will discuss the clinical outcome of some of these new therapies with a focus on ovarian and breast cancer. We will also discuss novel concepts in targeted therapy, the target of cancer stem cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Exercise, manual therapy, and use of booster sessions in physical therapy for knee osteoarthritis: a multi-center, factorial randomized clinical trial.

PubMed

Fitzgerald, G K; Fritz, J M; Childs, J D; Brennan, G P; Talisa, V; Gil, A B; Neilson, B D; Abbott, J H

2016-08-01

(1) Do treatment effects differ between participants receiving manual therapy (MT) with exercise compared to subjects who don't, (2) are treatment effects sustained better when participants receive booster sessions compared to those who don't over a one year period in subjects with knee osteoarthritis (KOA)? Multi-center, 2 × 2 factorial randomized clinical trial. 300 participants with knee OA were randomized to four groups: exercise-no boosters (Ex), exercise-with boosters (Ex+B), manual therapy+exercise-no boosters (MT+Ex), manual therapy+exercise-with boosters (MT+Ex+B). The primary outcome was the Western Ontario and McMaster osteoarthritis index (WOMAC) at 1 year. Secondary outcomes included knee pain, physical performance tests, and proportions of participants meeting treatment responder criteria. There were no differences between groups on the WOMAC at 1 year or on any performance-based measures. Secondary analyses indicated a) better scores on the WOMAC and greater odds of being a treatment responder at 9 weeks for participants receiving MT, b) greater odds of being a treatment responder at 1 year for participants receiving boosters. Exploratory interaction analysis suggested knee pain decreases for participants receiving boosters and increases for participants not receiving boosters from 9 weeks to 1 year. MT or use of boosters with exercise did not result in additive improvement in the primary outcome at 1 year. Secondary outcomes suggest MT may have some short term benefit, and booster sessions may improve responder status and knee pain at 1 year. However, the role of booster sessions remains unclear in sustaining treatment effects and warrants further study. gov (NCT01314183). Copyright © 2016 Osteoarthritis Research Society International. All rights reserved.

Validation of an educative manual for patients with head and neck cancer submitted to radiation therapy.

PubMed

Cruz, Flávia Oliveira de Almeida Marques da; Ferreira, Elaine Barros; Vasques, Christiane Inocêncio; Mata, Luciana Regina Ferreira da; Reis, Paula Elaine Diniz Dos

2016-06-14

develop the content and face validation of an educative manual for patients with head and neck cancer submitted to radiation therapy. descriptive methodological research. The Theory of Psychometrics was used for the validation process, developed by 15 experts in the theme area of the educative manual and by two language and publicity professionals. A minimum agreement level of 80% was considered to guarantee the validity of the material. the items addressed in the assessment tool of the educative manual were divided in three blocks: objectives, structure and format, and relevance. Only one item, related to the sociocultural level of the target public, obtained an agreement rate <80%, and was reformulated based on the participants' suggestions. All other items were considered appropriate and/or complete appropriate in the three blocks proposed: objectives - 92.38%, structure and form - 89.74%, and relevance - 94.44%. the face and content validation of the educative manual proposed were attended to. This can contribute to the understanding of the therapeutic process the head and neck cancer patient is submitted to during the radiation therapy, besides supporting clinical practice through the nursing consultation. validar o conteúdo e a aparência de manual educativo direcionado aos pacientes com câncer de cabeça e pescoço, submetidos à radioterapia. pesquisa metodológica, de caráter descritivo. Utilizou-se a Teoria da Psicometria para o processo de validação, o qual foi realizado por 15 peritos na área temática do manual educativo e por dois profissionais de letras e publicidade. Foi considerado o índice de concordância de, no mínimo, 80% para se garantir a validação do material. os itens abordados no instrumento de avaliação do manual educativo foram divididos em três blocos: objetivos, estrutura e apresentação, e relevância. Apenas um item, relacionado ao nível sociocultural do público-alvo, obteve índice de concordância <80%, tendo sido

Controversies in targeted therapy of adult T cell leukemia/lymphoma: ON target or OFF target effects?

PubMed

Nasr, Rihab; El Hajj, Hiba; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

2011-06-01

Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL.

Recent Advances in Targeted Therapy for Glioma.

PubMed

Lin, Lin; Cai, Jinquan; Jiang, Chuanlu

2017-01-01

Gliomas are the most common primary malignant brain tumors, which have a universally fatal outcome. Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment. This article reviewed the researches focused on the advanced strategies of various target therapies for improving the glioma treatment efficacy, and discussed the challenges and future directions for glioma therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Combining manual therapy with pain neuroscience education in the treatment of chronic low back pain: A narrative review of the literature.

PubMed

Puentedura, Emilio J; Flynn, Timothy

2016-07-01

Teaching people with chronic low back pain (CLBP) about the neurobiology and neurophysiology of their pain is referred to as pain neuroscience education (PNE). There is growing evidence that when PNE is provided to patients with chronic musculoskeletal pain, it can result in decreased pain, pain catastrophization, disability, and improved physical performance. Because the aim of PNE is to shift the patient's focus from the tissues in the low back as the source of their pain to the brain's interpretation of inputs, many clinicians could mistakenly believe that PNE should be a "hands-off," education-only approach. An argument can be made that by providing manual therapy or exercise to address local tissue pathology, the patient's focus could be brought back to the low back tissues as the source of their problem. In this narrative literature review, we present the case for a balanced approach that combines PNE with manual therapy and exercise by considering how manual therapy can also be incorporated for interventions with patients with CLBP. We propose that as well as producing local mechanical effects, providing manual therapy within a PNE context can be seen as meeting or perhaps enhancing patient expectations, and also refreshing or sharpening body schema maps within the brain. Ideally, all of this should lead to better outcomes in patients with CLBP.

Effectiveness of manual physical therapy to the cervical spine in the management of lateral epicondylalgia: a retrospective analysis.

PubMed

Cleland, Joshua A; Whitman, Julie M; Fritz, Julie M

2004-11-01

Retrospective ex-post facto design. To retrospectively review the management of patients with lateral epicondylalgia, and to compare self-reported outcomes to assess the potential benefit of manual physical therapy to the cervical spine. It has been postulated that dysfunction of the cervical spine may contribute to the symptoms associated with lateral epicondylalgia; however, the literature assessing the effectiveness of manual physical therapy to the cervicothoracic region in this patient population has been inconclusive. Documentation and analysis of outcomes of management strategies focusing on the cervical spine may lead to determining the most effective and efficient clinical practices. Of the 213 charts reviewed, 112 satisfied inclusion-exclusion criteria and were divided into 2 groups: those who received treatment solely directed at the elbow (local management [LM]), or those who received treatment directed at the elbow and cervical manual therapy (LM+C). Telephone follow-up interviews were used to determine the number of successful outcomes. Percentages of successful outcomes in each group were compared using chi-square analysis. An independent samples t test was used to compare the total number of visits per group. Sixty-one of the 112 patients were in the LM group, while 51 received LM+C. Seventy five percent of the patients available for follow-up in the LM group and 80% in the LM+C group reported a successful outcome. Patients in the LM group received a greater number of visits (mean, 9.7; SD, 2.4) than patients in the LM+C group (mean, 5.6; SD, 1.7; P<.01). The results of this retrospective review suggest that most patients had successful outcomes regardless of the inclusion of manual therapy interventions to the cervical spine. The LM+C group achieved the successful long-term outcome in significantly fewer visits.

Advances of Molecular Targeted Therapy in Gastric Cancer.

PubMed

Cetin, Bulent; Gumusay, Ozge; Cengiz, Mustafa; Ozet, Ahmet

2016-06-01

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

Therapist Adherence and Competence with Manualized Cognitive-Behavioral Therapy for PTSD Delivered via Videoconferencing Technology

ERIC Educational Resources Information Center

Frueh, B. Christopher; Monnier, Jeannine; Grubaugh, Anouk L.; Elhai, Jon D.; Yim, Eunsil; Knapp, Rebecca

2007-01-01

Using secondary analyses from a randomized trial comparing the effectiveness of manualized cognitive-behavioral therapy for posttraumatic stress disorder, we compared ratings of therapist competency and adherence between two service delivery modes: telepsychiatry (TP) and same room (SR). Patients were 38 male treatment-seeking veterans recruited…

Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

PubMed Central

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-01

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration. PMID:25606974

Bacteriophage-derived vectors for targeted cancer gene therapy.

PubMed

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-19

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration.

Controversies in Targeted Therapy of Adult T Cell Leukemia/Lymphoma: ON Target or OFF Target Effects?

PubMed Central

Nasr, Rihab; Hajj, Hiba El; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

2011-01-01

Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL. PMID:21994752

Mucin-based targeted pancreatic cancer therapy.

PubMed

Torres, Maria P; Chakraborty, Subhankar; Souchek, Joshua; Batra, Surinder K

2012-01-01

The prognosis of pancreatic cancer (PC) patients is very poor with a five-year survival of less than 5%. One of the major challenges in developing new therapies for PC is the lack of expression of specific markers by pancreatic tumor cells. Mucins are heavily Oglycosylated proteins characterized by the presence of short stretches of amino acid sequences repeated several times in tandem. The expression of several mucins including MUC1, MUC4, MUC5AC, and MUC16 is strongly upregulated in PC. Recent studies have also demonstrated a link between the aberrant expression and differential overexpression of mucin glycoproteins to the initiation, progression, and poor prognosis of the disease. These studies have led to increasing recognition of mucins as potential diagnostic markers and therapeutic targets in PC. In this focused review we present an overview of the therapies targeting mucins in PC, including immunotherapy (i.e. vaccines, antibodies, and radioimmunoconjugates), gene therapy, and other novel therapeutic strategies.

Active versus passive adverse event reporting after pediatric chiropractic manual therapy: study protocol for a cluster randomized controlled trial.

PubMed

Pohlman, Katherine A; Carroll, Linda; Tsuyuki, Ross T; Hartling, Lisa; Vohra, Sunita

2017-12-01

Patient safety performance can be assessed with several systems, including passive and active surveillance. Passive surveillance systems provide opportunity for health care personnel to confidentially and voluntarily report incidents, including adverse events, occurring in their work environment. Active surveillance systems systematically monitor patient encounters to seek detailed information about adverse events that occur in work environments; unlike passive surveillance, active surveillance allows for collection of both numerator (number of adverse events) and denominator (number of patients seen) data. Chiropractic manual therapy is commonly used in both adults and children, yet few studies have been done to evaluate the safety of chiropractic manual therapy for children. In an attempt to evaluate this, this study will compare adverse event reporting in passive versus active surveillance systems after chiropractic manual therapy in the pediatric population. This cluster randomized controlled trial aims to enroll 70 physicians of chiropractic (unit of randomization) to either passive or active surveillance system to report adverse events that occur after treatment for 60 consecutive pediatric (13 years of age and younger) patient visits (unit of analysis). A modified enrollment process with a two-phase consent procedure will be implemented to maintain provider blinding and minimize dropouts. The first phase of consent is for the provider to confirm their interest in a trial investigating the safety of chiropractic manual therapy. The second phase ensures that they understand the specific requirements for the group to which they were randomized. Percentages, incidence estimates, and 95% confidence intervals will be used to describe the count of reported adverse events in each group. The primary outcome will be the number and quality of the adverse event reports in the active versus the passive surveillance group. With 80% power and 5% one-sided significance

Imatinib: A Breakthrough of Targeted Therapy in Cancer

PubMed Central

Iqbal, Naveed

2014-01-01

Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology. PMID:24963404

Improving patient outcomes to targeted therapies in melanoma.

PubMed

Eroglu, Zeynep; Smalley, Keiran S M; Sondak, Vernon K

2016-06-01

The arrival of targeted therapies has led to significant improvements in clinical outcomes for patients with BRAFV600 mutated advanced melanoma over the past five years. In several clinical trials, BRAF and MEK inhibitors have shown improvement in progression free and overall survival, along with much higher tumor response rates in comparison to chemotherapy, with the combination of these drugs superior to monotherapy. These agents are also being tested in earlier-stage patients, in addition to alternative dosing regimens and in combinations with other therapeutics. Efforts are also ongoing to expand the success found with targeted therapies to other subtypes of melanoma, including NRAS and c-kit mutated melanomas, uveal melanomas, and BRAF/NRAS wild type melanomas. Expert Commentary: We aim to provide an overview of clinical outcomes with targeted therapies in melanoma patients.

Manual lymphatic drainage therapy in patients with breast cancer related lymphoedema.

PubMed

Martín, Marta López; Hernández, Miguel A; Avendaño, Cristina; Rodríguez, Francisco; Martínez, Helena

2011-03-09

Lymphoedema is a common and troublesome condition that develops following breast cancer treatment. The aim of this study is to analyze the effectiveness of Manual Lymphatic Drainage in the treatment of postmastectomy lymphoedema in order to reduce the volume of lymphoedema and evaluate the improvement of the concomitant symptomatology. A randomized, controlled clinical trial in 58 women with post-mastectomy lymphoedema. The control group includes 29 patients with standard treatment (skin care, exercise and compression measures, bandages for one month and, subsequently, compression garments). The experimental group includes 29 patients with standard treatment plus Manual Lymphatic Drainage. The therapy will be administered daily for four weeks and the patient's condition will be assessed one, three and six months after treatment.The primary outcome parameter is volume reduction of the affected arm after treatment, expressed as a percentage. Secondary outcome parameters include: duration of lymphoedema reduction and improvement of the concomitant symptomatology (degree of pain, sensation of swelling and functional limitation in the affected extremity, subjective feeling of being physically less attractive and less feminine, difficulty looking at oneself naked and dissatisfaction with the corporal image). The results of this study will provide information on the effectiveness of Manual Lymphatic Drainage and its impact on the quality of life and physical limitations of these patients. ClinicalTrials (NCT): NCT01152099.

Target marketing strategies for occupational therapy entrepreneurs.

PubMed

Kautzmann, L N; Kautzmann, F N; Navarro, F H

1989-01-01

Understanding marketing techniques is one of the skills needed by successful entre renews. Target marketing is an effective method for occupational therapy entrepreneurs to use in determining when and where to enter the marketplace. The two components of target marketing, market segmentation and the development of marketing mix strategies for each identified market segment, are described. The Profife of Attitudes Toward Health Care (PATH) method of psychographic market segmentation of health care consumers is presented. Occupational therapy marketing mix strategies for each PATH consumer group are delineated and compatible groupings of market segments are suggested.

Evaluation of three automatic oxygen therapy control algorithms on ventilated low birth weight neonates.

PubMed

Morozoff, Edmund P; Smyth, John A

2009-01-01

Neonates with under developed lungs often require oxygen therapy. During the course of oxygen therapy, elevated levels of blood oxygenation, hyperoxemia, must be avoided or the risk of chronic lung disease or retinal damage is increased. Low levels of blood oxygen, hypoxemia, may lead to permanent brain tissue damage and, in some cases, mortality. A closed loop controller that automatically administers oxygen therapy using 3 algorithms - state machine, adaptive model, and proportional integral derivative (PID) - is applied to 7 ventilated low birth weight neonates and compared to manual oxygen therapy. All 3 automatic control algorithms demonstrated their ability to improve manual oxygen therapy by increasing periods of normoxemia and reducing the need for manual FiO(2) adjustments. Of the three control algorithms, the adaptive model showed the best performance with 0.25 manual adjustments per hour and 73% time spent within target +/- 3% SpO(2).

Effects of exercise and manual therapy on pain associated with hip osteoarthritis: a systematic review and meta-analysis.

PubMed

Beumer, Lucy; Wong, Jennie; Warden, Stuart J; Kemp, Joanne L; Foster, Paul; Crossley, Kay M

2016-04-01

To explore the effects of exercise (water-based or land-based) and/or manual therapies on pain in adults with clinically and/or radiographically diagnosed hip osteoarthritis (OA). A systematic review and meta-analysis was performed, with patient reported pain assessed using a visual analogue scale (VAS) or the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. Data were grouped by follow-up time (0-3 months=short term; 4-12 months=medium term and; >12 months=long term), and standardised mean differences (SMD) with 95% CIs were used to establish intervention effect sizes. Study quality was assessed using modified PEDro scores. 19 trials were included. Four studies showed short-term benefits favouring water-based exercise over minimal control using the WOMAC pain subscale (SMD -0.53, 95% CI -0.96 to -0.10). Six studies supported a short-term benefit of land-based exercise compared to minimal control on VAS assessed pain (SMD -0.49, 95% CI -0.70 to -0.29). There were no medium (SMD -0.23, 95% CI -0.48 to 0.03) or long (SMD -0.22, 95% CI -0.51 to 0.06) term benefits of exercise therapy, or benefit of combining exercise therapy with manual therapy (SMD -0.38, 95% CI -0.88 to 0.13) when compared to minimal control. Best available evidence indicates that exercise therapy (whether land-based or water-based) is more effective than minimal control in managing pain associated with hip OA in the short term. Larger high-quality RCTs are needed to establish the effectiveness of exercise and manual therapies in the medium and long term. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Placebo Mechanisms of Manual Therapy: A Sheep in Wolf's Clothing?

PubMed

Bialosky, Joel E; Bishop, Mark D; Penza, Charles W

2017-05-01

When a physical therapist provides a manual therapy (MT) intervention for a patient presenting with pain and the patient experiences a positive clinical outcome, we cannot answer as to why this occurs. Would we continue to devote valuable time and financial resources to learning and improving our skills in providing MT interventions if the related clinical outcomes were placebo responses? In this Viewpoint, the authors conceptualize placebo as an active and important mechanism of MT and argue that placebo mechanisms deserve consideration as an important component of the treatment effect. J Orthop Sports Phys Ther 2017;47(5):301-304. doi:10.2519/jospt.2017.0604.

Immediate Changes After Manual Therapy in Patients With Persistent, Nonspecific Back Pain: A Randomized Controlled Trial.

PubMed

Espí-López, Gemma Victoria; Ruescas-Nicolau, Maria-Arantzazu; Sanchez-Sanchez, M Luz; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Marques-Sule, Elena

2018-02-10

Context • Thoracic manipulation decreases pain and disability. However, when such manipulation is contraindicated, the use of other manual techniques based on the regional interdependence of the thoracic spine, upper ribs, and shoulders is an alternative approach. Objective • The study intended to investigate the immediate changes resulting from 3 manual therapy treatments on spinal mobility, flexibility, comfort, and pain perception in patients with persistent, nonspecific back pain as well as changes in their sense of physical well-being and their perception of change after treatment. Design • The study was a randomized, double-blind, controlled trial. Setting • The study took place in the Department of Physiotherapy of the Faculty of Physiotherapy at the University of Valencia (Valencia, Spain). Participants • Participants were 112 individuals from the community-56.6% female, with a mean age of 21.8 ± 0.2 y-who had persistent, nonspecific back pain. Intervention • Participants were randomly assigned to 1 of 3 groups, receiving (1) neurolymphatic therapy (NL group), (2) articulatory spinal manual therapy (AS group), or (3) articulatory costal manual therapy (AC group). Outcome Measures • Cervical mobility, lumbar flexibility, comfort, pain perception, and physical well-being were assessed at baseline and immediately postintervention. Perception of change was evaluated postintervention. Results • Between baseline and postintervention, the AC group showed a significant increase in cervical flexion (P = .010), whereas the NL and AS groups improved in lumbar flexibility, P = .047 and P = .012, respectively. For that period, significant changes were found in lumbar comfort for the AS group (P < .001) and the NL group (P < .026) and in thoracic comfort (P < .001) for the AC group. All groups improved in physical well-being and pain perception (P < .05). Changes in thoracic comfort, lumbar comfort, and physical well-being differed among the groups, with

Health Occupations--Respiration Therapy Technician. Kit No. 66. Instructor's Manual [and] Student Learning Activity Guide.

ERIC Educational Resources Information Center

Jackson, Janette

An instructor's manual and student activity guide on respiration therapy technician are provided in this set of prevocational education materials which focuses on the vocational area of health occupations. (This set of materials is one of ninety-two prevocational education sets arranged around a cluster of seven vocational offerings: agriculture,…

Treating Small Bowel Obstruction with a Manual Physical Therapy: A Prospective Efficacy Study

PubMed Central

Rice, Amanda D.; Patterson, Kimberley; Reed, Evette D.; Wurn, Belinda F.; Klingenberg, Bernhard; King, C. Richard; Wurn, Lawrence J.

2016-01-01

Small bowel obstructions (SBOs) caused by adhesions are a common, often life-threatening postsurgical complication with few treatment options available for patients. This study examines the efficacy of a manual physical therapy treatment regimen on the pain and quality of life of subjects with a history of bowel obstructions due to adhesions in a prospective, controlled survey based study. Changes in six domains of quality of life were measured via ratings reported before and after treatment using the validated Small Bowel Obstruction Questionnaire (SBO-Q). Improvements in the domains for pain (p = 0.0087), overall quality of life (p = 0.0016), and pain severity (p = 0.0006) were significant when average scores before treatment were compared with scores after treatment. The gastrointestinal symptoms (p = 0.0258) domain was marginally significant. There was no statistically significant improvement identified in the diet or medication domains in the SBO-Q for this population. Significant improvements in range of motion in the trunk (p ≤ 0.001), often limited by adhesions, were also observed for all measures. This study demonstrates in a small number of subjects that this manual physical therapy protocol is an effective treatment option for patients with adhesive small bowel obstructions as measured by subject reported symptoms and quality of life. PMID:26989690

Manual therapy in the treatment of ankle hemophilic arthropathy. A randomized pilot study.

PubMed

Cuesta-Barriuso, Rubén; Gómez-Conesa, Antonia; López-Pina, José-Antonio

2014-11-01

Although physiotherapy has demonstrated effectiveness in preventing ankle arthropathy compared to prophylaxis treatment from early ages, there have been no conclusive studies examining physiotherapy intervention once hemophilic arthropathy of the ankle has been established. The aim of this study was to evaluate the effectiveness of two physiotherapy interventions, in patients with hemophilic arthropathy of the ankle that had not been operated on previously. Nine patients with hemophilia (mean age of 35.7 SD 11.9 years) were randomized to a mobilization group (n = 5) and manual therapy group (n = 4). The two physiotherapy interventions were: (1) passive mobilization and stretching; and (2) manual orthopaedic therapy, both with proprioception training. The study lasted for six weeks, with two sessions a week. Ankle mobility and pain perception, lower limb proprioception and quality of life were the outcome measures. Both treatments improved all ankle movements (p < 0.05). The treatment with passive mobilizations also improved the perception of pain and quality of life. Six months later, both groups still had improved articular movement with the exception of plantar flexion and continued to perceive less pain. Both physiotherapy interventions improved the range of movement and lessened pain in patients with ankle arthropathy. No haemarthrosis was recorded during treatment or during the follow-up period.

Economic evaluation of manual therapy for musculoskeletal diseases: a protocol for a systematic review and narrative synthesis of evidence.

PubMed

Kim, Chang-Gon; Mun, Su-Jeong; Kim, Ka-Na; Shin, Byung-Cheul; Kim, Nam-Kwen; Lee, Dong-Hyo; Lee, Jung-Han

2016-05-13

Manual therapy is the non-surgical conservative management of musculoskeletal disorders using the practitioner's hands on the patient's body for diagnosing and treating disease. The aim of this study is to systematically review trial-based economic evaluations of manual therapy relative to other interventions used for the management of musculoskeletal diseases. Randomised clinical trials (RCTs) on the economic evaluation of manual therapy for musculoskeletal diseases will be included in the review. The following databases will be searched from their inception: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Econlit, Mantis, Index to Chiropractic Literature, Science Citation Index, Social Science Citation Index, Allied and Complementary Medicine Database (AMED), Cochrane Database of Systematic Reviews (CDSR), National Health Service Database of Abstracts of Reviews of Effects (NHS DARE), National Health Service Health Technology Assessment Database (NHS HTA), National Health Service Economic Evaluation Database (NHS EED), CENTRAL, five Korean medical databases (Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Service System (RISS), DBPIA, Korean Traditional Knowledge Portal (KTKP) and KoreaMed) and three Chinese databases (China National Knowledge Infrastructure (CNKI), VIP and Wanfang). The evidence for the cost-effectiveness, cost-utility and cost-benefit of manual therapy for musculoskeletal diseases will be assessed as the primary outcome. Health-related quality of life and adverse effects will be assessed as secondary outcomes. We will critically appraise the included studies using the Cochrane risk of bias tool and the Drummond checklist. Results will be summarised using Slavin's qualitative best-evidence synthesis approach. The results of the study will be disseminated via a peer-reviewed journal and/or conference presentations

Group cognitive-behavioral therapy for depression in Spanish: culture-sensitive manualized treatment in practice.

PubMed

Aguilera, Adrian; Garza, Monica J; Muñoz, Ricardo F

2010-08-01

The authors applied cognitive-behavioral therapy (CBT) for depression using the Healthy Management of Reality treatment manual. This 16-week group treatment comprised four 4-week modules: thoughts (cognitive restructuring), activities (behavioral activation), people (interpersonal skills training), and health (addresses physical health and depression). They illustrated the use of the culture-sensitive treatment manuals by way of the member characteristics and clinical process of a Spanish-language CBT group for depression. They highlighted the challenges and satisfactions of working with a Spanish-speaking population in the public sector, and focused on how culture and socioeconomic status influence patients, and how to adapt treatment to these factors. Last, they demonstrated how technological advances integrate with culture-sensitive, evidence-based treatments to better serve this population and reduce disparities.

Case report: manualized trauma-focused cognitive behavioral therapy with an unaccompanied refugee minor girl.

PubMed

Unterhitzenberger, Johanna; Rosner, Rita

2016-01-01

There is uncertainty whether young traumatized refugees should be treated with culturally adapted psychotherapy or with an evidence-based western approach. As yet, empirical studies on culturally adapted treatments for unaccompanied young refugees in industrialized host countries are not available. Studies do, however, suggest that trauma-focused treatment is promising for this group. We describe the treatment of an unaccompanied refugee minor girl with posttraumatic stress disorder (PTSD) who underwent manualized trauma-focused cognitive behavioral therapy (TF-CBT; Cohen, Mannarino, & Deblinger, 2006). A 17-year-old girl from East Africa, who came to Germany without a caregiver, was treated for PTSD resulting from several traumatic experiences and losses in her home country and while fleeing. She lived in a group home for adolescents. Baseline, post, and follow-up data are reported. The girl participated in 12 sessions of manualized TF-CBT. Her caregiver from the youth services received another 12 sessions in line with the treatment manual. Symptoms decreased in a clinically significant manner; at the end of the treatment, the girl was deemed to have recovered from PTSD. Treatment success remained stable over 6 months. Manualized TF-CBT is feasible for young refugees without significant cultural adaptations. It can, however, be seen as culturally sensitive.

A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

PubMed

Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

Choosing a therapy electron accelerator target.

PubMed

Hutcheon, R M; Schriber, S O; Funk, L W; Sherman, N K

1979-01-01

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...AND SUBTITLE Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Effects of manual therapy on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly: a randomised controlled pilot study.

PubMed

Cabrera-Martos, I; Valenza, M C; Valenza-Demet, G; Benítez-Feliponi, A; Robles-Vizcaíno, C; Ruiz-Extremera, A

2016-11-01

Despite growing evidence regarding nonsynostotic plagiocephaly and their repercussions on motor development, there is little evidence to support the use of manual therapy as an adjuvant option. The aim of this study was to evaluate the effects of a therapeutic approach based on manual therapy as an adjuvant option on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly. This is a randomised controlled pilot study. The study was conducted at a university hospital. Forty-six infants with severe nonsynostotic plagiocephaly (types 4-5 of the Argenta scale) referred to the Early Care and Monitoring Unit were randomly allocated to a control group receiving standard treatment (repositioning and an orthotic helmet) or to an experimental group treated with manual therapy added to standard treatment. Infants were discharged when the correction of the asymmetry was optimal taken into account the previous clinical characteristics. The outcome measures were treatment duration and motor development assessed with the Alberta Infant Motor Scale (AIMS) at baseline and at discharge. Asymmetry after the treatment was minimal (type 0 or 1 according to the Argenta scale) in both groups. A comparative analysis showed that treatment duration was significantly shorter (p < 0.001) in the experimental group (109.84 ± 14.45 days) compared to the control group (148.65 ± 11.53 days). The motor behaviour was normal (scores above the 16th percentile of the AIMS) in all the infants after the treatment. Manual therapy added to standard treatment reduces the treatment duration in infants with severe nonsynostotic plagiocephaly.

Molecular targeting agents in cancer therapy: science and society.

PubMed

Shaikh, Asim Jamal

2012-01-01

The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.

The effectiveness of manual physical therapy interventions in pediatric patients with anterior hip pain: a retrospective study.

PubMed

Galleher, Mindy; Crowe, Briana; Selhorst, Mitchell

2017-12-01

The purposes of this study were to: (1) assess the benefit of adding manual therapy (MT) to physical therapy care in pediatric patients with anterior hip pain; (2) assess the relative risk of adverse reactions when MT is used; and (3) report the types of MT used. This study was a retrospective chart review of patients treated in a hospital-based sports medicine clinic. The charts of 201 patients (mean age = 14.23 ± 2.15 years) met the inclusion criteria and were reviewed. Patients were grouped into those who received MT during their episode of care, and those who did not. Pain efficiency (change in pain/number of visits), number and type of adverse reactions, as well as frequency and type of manual therapy interventions used, were the outcomes of interest. The mean pain efficiency was significantly less if manual therapy was performed (MT = 0.60 [95% CI 0.47-0.72], no MT = 0.80 [95% CI 0.71-0.90] p  = 0.01). There was no significant difference between groups in risk of adverse reactions (MT = 5, no MT = 5). The number of visits was significantly different between groups (MT = 9.43 ± 3.9 sessions, and no MT = 7.6 ± 5.2 sessions). MT did not increase the risk of an adverse reaction in pediatric patients with anterior hip pain. While it appears to be a safe intervention, it did not improve pain efficiency or patient adherence. Future research should be performed to assess the effectiveness of MT, when performed by skilled therapists, in pediatric patients with hip pain in a controlled manner. Level of Evidence: 3b.

Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice.

PubMed

Nijs, Jo; Van Houdenhove, Boudewijn; Oostendorp, Rob A B

2010-04-01

Central sensitization plays an important role in the pathophysiology of numerous musculoskeletal pain disorders, yet it remains unclear how manual therapists can recognize this condition. Therefore, mechanism based clinical guidelines for the recognition of central sensitization in patients with musculoskeletal pain are provided. By using our current understanding of central sensitization during the clinical assessment of patients with musculoskeletal pain, manual therapists can apply the science of nociceptive and pain processing neurophysiology to the practice of manual therapy. The diagnosis/assessment of central sensitization in individual patients with musculoskeletal pain is not straightforward, however manual therapists can use information obtained from the medical diagnosis, combined with the medical history of the patient, as well as the clinical examination and the analysis of the treatment response in order to recognize central sensitization. The clinical examination used to recognize central sensitization entails the distinction between primary and secondary hyperalgesia. Copyright 2009 Elsevier Ltd. All rights reserved.

Molecular mechanisms for vascular complications of targeted cancer therapies.

PubMed

Gopal, Srila; Miller, Kenneth B; Jaffe, Iris Z

2016-10-01

Molecularly targeted anti-cancer therapies have revolutionized cancer treatment by improving both quality of life and survival in cancer patients. However, many of these drugs are associated with cardiovascular toxicities that are sometimes dose-limiting. Moreover, the long-term cardiovascular consequences of these drugs, some of which are used chronically, are not yet known. Although the scope and mechanisms of the cardiac toxicities are better defined, the mechanisms for vascular toxicities are only beginning to be elucidated. This review summarizes what is known about the vascular adverse events associated with three classes of novel anti-cancer therapies: vascular endothelial growth factor (VEGF) inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in myeloma therapeutics. Three of the best described vascular toxicities are reviewed including hypertension, increased risk of acute cardiovascular ischaemic events and arteriovenous thrombosis. The available data regarding the mechanism by which each therapy causes vascular complication are summarized. When data are limited, potential mechanisms are inferred from the known effects of inhibiting each target on vascular cell function and disease. Enhanced understanding of the molecular mechanisms of vascular side effects of targeted cancer therapy is necessary to effectively manage cancer patients and to design safer targeted cancer therapies for the future. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Exercise, Manual Therapy, and Booster Sessions in Knee Osteoarthritis: Cost-Effectiveness Analysis From a Multicenter Randomized Controlled Trial.

PubMed

Bove, Allyn M; Smith, Kenneth J; Bise, Christopher G; Fritz, Julie M; Childs, John; Brennan, Gerard P; Abbott, J Haxby; Fitzgerald, G Kelley

2018-01-01

Limited information exists regarding the cost-effectiveness of rehabilitation strategies for individuals with knee osteoarthritis (OA). The study objective was to compare the cost-effectiveness of 4 different combinations of exercise, manual therapy, and booster sessions for individuals with knee OA. This economic evaluation involved a cost-effectiveness analysis performed alongside a multicenter randomized controlled trial. The study took place in Pittsburgh, Pennsylvania; Salt Lake City, Utah; and San Antonio, Texas. The study participants were 300 individuals taking part in a randomized controlled trial investigating various physical therapy strategies for knee OA. Participants were randomized into 4 treatment groups: exercise only (EX), exercise plus booster sessions (EX+B), exercise plus manual therapy (EX+MT), and exercise plus manual therapy and booster sessions (EX+MT+B). For the 2-year base case scenario, a Markov model was constructed using the United States societal perspective and a 3% discount rate for costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated to compare differences in cost per QALY gained among the 4 treatment strategies. In the 2-year analysis, booster strategies (EX+MT+B and EX+B) dominated no-booster strategies, with both lower health care costs and greater effectiveness. EX+MT+B had the lowest total health care costs. EX+B cost ${\\$}$1061 more and gained 0.082 more QALYs than EX+MT+B, for an incremental cost-effectiveness ratio of ${\\$}$12,900/QALY gained. The small number of total knee arthroplasty surgeries received by individuals in this study made the assessment of whether any particular strategy was more successful at delaying or preventing surgery in individuals with knee OA difficult. Spacing exercise-based physical therapy sessions over 12 months using periodic booster sessions was less costly and more effective over 2 years than strategies not containing booster sessions for

Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

PubMed Central

Chen, Lian; Cui, Hengmin

2015-01-01

Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to cells by specific transporters and converted to glutamate by glutaminase. There are currently several drugs that target glutaminase under development or clinical trials. Also, glutamine metabolism restriction has been proved to be effective in inhibiting tumor growth both in vivo and vitro through inducing apoptosis, growth arrest and/or autophagy. Here, we review recent researches about glutamine metabolism in cancer, and cell death induced by targeting glutamine, and their potential roles in cancer therapy. PMID:26402672

Efficacy of manual and manipulative therapy in the perception of pain and cervical motion in patients with tension-type headache: a randomized, controlled clinical trial.

PubMed

Espí-López, Gemma V; Gómez-Conesa, Antonia

2014-03-01

The purpose of this study was to evaluate the efficacy of manipulative and manual therapy treatments with regard to pain perception and neck mobility in patients with tension-type headache. A randomized clinical trial was conducted on 84 adults diagnosed with tension-type headache. Eighty-four subjects were enrolled in this study: 68 women and 16 men. Mean age was 39.76 years, ranging from 18 to 65 years. A total of 57.1% were diagnosed with chronic tension-type headache and 42.9% with tension-type headache. Participants were divided into 3 treatment groups (manual therapy, manipulative therapy, a combination of manual and manipulative therapy) and a control group. Four treatment sessions were administered during 4 weeks, with posttreatment assessment and follow-up at 1 month. Cervical ranges of motion pain perception, and frequency and intensity of headaches were assessed. All 3 treatment groups showed significant improvements in the different dimensions of pain perception. Manual therapy and manipulative treatment improved some cervical ranges of motion. Headache frequency was reduced with manipulative treatment (P < .008). Combined treatment reported improvement after the treatment (P < .000) and at follow-up (P < .002). Pain intensity improved after the treatment and at follow-up with manipulative therapy (P < .01) and combined treatment (P < .01). Both treatments, administered both separately and combined together, showed efficacy for patients with tension-type headache with regard to pain perception. As for cervical ranges of motion, treatments produced greater effect when separately administered.

Group Cognitive-Behavioral Therapy for Depression in Spanish: Culture-Sensitive Manualized Treatment in Practice

PubMed Central

Aguilera, Adrian; Garza, Monica J.; Muñoz, Ricardo F.

2014-01-01

The authors applied cognitive-behavioral therapy (CBT) for depression using the Healthy Management of Reality treatment manual. This 16-week group treatment comprised four 4-week modules: thoughts (cognitive restructuring), activities (behavioral activation), people (interpersonal skills training), and health (addresses physical health and depression). They illustrated the use of the culture-sensitive treatment manuals by way of the member characteristics and clinical process of a Spanish-language CBT group for depression. They highlighted the challenges and satisfactions of working with a Spanish-speaking population in the public sector, and focused on how culture and socioeconomic status influence patients, and how to adapt treatment to these factors. Last, they demonstrated how technological advances integrate with culture-sensitive, evidence-based treatments to better serve this population and reduce disparities. PMID:20549680

Oral Rehydration Therapy and the Control of Diarrheal Diseases. Training for Development. Peace Corps Information Collection & Exchange Training Manual No. T-34.

ERIC Educational Resources Information Center

Clark, Mari; And Others

This manual was developed to train Peace Corps volunteers and other community health workers in oral rehydration therapy (ORT) and the control of diarrheal diseases. Using a competency-based format, the manual contains six training modules (organized in 22 sessions) that focus on interrelated health education and technical content areas. Each…

Targeted therapies in the treatment of urothelial cancers.

PubMed

Aragon-Ching, Jeanny B; Trump, Donald L

2017-07-01

Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiotoxicity of novel HER2-targeted therapies.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Altundag, Kadri

2013-08-01

Trastuzumab, an anti-HER2 humanized monoclonal antibody, is the standard treatment for both early and metastatic HER2-positive breast cancer. In addition to other chemotherapeutic agents, trastuzumab significantly improves response rate and survival in HER2-positive early and metastatic breast cancer. Although it is well known that trastuzumab therapy is closely associated with both symptomatic and asymptomatic cardiotoxicity, less is known about novel HER2-targeted therapies. The aim of this review is to discuss the cardiac safety data from recent studies of novel anti-HER2 drugs other than trastuzumab. Novel HER2-targeted therapies showed favorable results in HER2 positive metastatic breast cancer patients. Pubmed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched until January 2013 using the following search keywords; 'trastuzumab, trastuzumab cardiotoxicity, HER-2 targeted therapies, lapatinib, pertuzumab, trastuzumab emtansine, afatinib and neratinib'; papers which were considered relevant for the aim of this review were selected by the authors. Lapatinib, pertuzumab, T-DM1, neratinib and afatinib molecules are evaluated in the study. In a comprehensive analysis, 3689 lapatinib treated patients enrolled in 49 trials; asymptomatic cardiac events were reported in 53 patients (1.4%) and symptomatic grade III and IV systolic dysfunction was observed only in 7 patients (0.2%) treated with lapatinib. In phase I-III trials of pertuzumab, cardiac dysfunction was seen in 4.5-14.5% of patients with pertuzumab treatment and cardiac dysfunction was usually grade I and II. Cardiotoxicity of pertuzumab was usually reported with the trastuzumab combination and no additive cardiotoxicity was reported with addition of pertuzumab to trastuzumab. T-DM1 had a better safety profile compared to trastuzumab, no significant cardiotoxicity was observed with T-DM1 in heavily pre-treated patients. In the EMILIA study, only in 1.7% of patients in the T

Manual de Adiestramiento sobre Terapia de Rehidratacion Oral y Control de las Enfermedades Diarreicas (Oral Rehydration Therapy and the Control of Diarrheal Diseases). Training for Development. Peace Corps Information Collection & Exchange Training Manual No. T-53.

ERIC Educational Resources Information Center

Clark, Mari; And Others

This Spanish-language manual was developed to train Peace Corps volunteers and other community health workers in Spanish-speaking countries in oral rehydration therapy (ORT) and the control of diarrheal diseases. Using a competency-based format, the manual contains three training modules (organized in seven sessions) that focus on interrelated…

Manual therapy and therapeutic exercise in patient with symptomatic cervical spondylotic myelopathy: a case report.

PubMed

Almeida, Gabriel Peixoto Leão; Carneiro, Kysia Karine Almeida; Marques, Amélia Pasqual

2013-10-01

Cervical spondylotic myelopathy (CSM) is caused by narrowing of the cervical spinal canal, although surgical decompression is an obvious indication for spinal cord stenosis, there are not enough data to determine that surgery is the most indicated intervention for milder forms. The purpose of the present case report was to describe the outcomes results of the physical therapy treatment with emphasis on manual therapy and therapeutic exercise for a patient with CSM. A 58-year-old male patient attended the physical therapy clinic due to pain and paresthesia in the upper and lower limbs. The magnetic resonance imaging was compatible with spondylotic myelopathy. Following physical therapy treatment, the patient exhibited an improvement in functional capacity (triangle step test and timed 10-m walk), pain, paresthesia, mJOA scale and Neck Disability Index. Based on the lack of rapid evolution of neurological impairment, physical therapy treatment was indicated, which achieved satisfactory results. Copyright © 2013 Elsevier Ltd. All rights reserved.

A manual therapy and exercise approach to meralgia paresthetica in pregnancy: a case report

PubMed Central

Skaggs, Clayton D.; Winchester, Brett A.; Vianin, Michael; Prather, Heidi

2006-01-01

Abstract Objective To present a case of a pregnant patient with meralgia paresthetica who improved using manual therapy and exercise procedures. Clinical Features A 22-year-old patient in the sixteenth week of pregnancy had low back pain, bilateral anterolateral thigh paresthesia and groin pain for a duration of 1 month. She had no motor deficits in either lower extremity and her reflexes were intact. As a standard clinic procedure, a battery of functional tests were performed including: active straight leg raise, long dorsal ligament test, and the pelvic pain provocation procedure. Based on her clinical history and physical responses to the aforementioned functional tests, the diagnosis of meralgia paresthetica was deduced. Intervention and Outcome Treatment was provided at 6 visits over a 6-week period where the patient underwent evaluation, manual intervention, and exercise prescription. Active Release Technique (ART) was performed to the restricted right sacroiliac (SIJ) complex and quadratus lumborum muscles. ART and post-isometric relaxation were applied to the illiopsoas muscles. The home exercise program consisted of pelvic/low back mobility, stabilization and relaxation exercises. After 6 treatments, the patient reported complete resolution of low back pain and left lower extremity symptoms and a 90% improvement in the right thigh symptoms. At her one-year follow-up, the patient reported no further complications and the absence of pain. Conclusions Manual therapy and exercises may serve as an effective treatment protocol for pregnant patients experiencing low back pain complicated by paresthesia. Because these conservative procedures offer a low-risk intervention, additional clinical studies are warranted to further study this treatment. PMID:19674679

The immediate effect of soft tissue manual therapy intervention on lung function in severe chronic obstructive pulmonary disease

PubMed Central

Cruz-Montecinos, Carlos; Godoy-Olave, Diego; Contreras-Briceño, Felipe A; Gutiérrez, Paulina; Torres-Castro, Rodrigo; Miret-Venegas, Leandro; Engel, Roger M

2017-01-01

Background and objective In chronic obstructive pulmonary disease (COPD), accessory respiratory muscles are recruited as a compensatory adaptation to changes in respiratory mechanics. This results in shortening and overactivation of these and other muscles. Manual therapy is increasingly being investigated as a way to alleviate these changes. The aim of this study was to measure the immediate effect on lung function of a soft tissue manual therapy protocol (STMTP) designed to address changes in the accessory respiratory muscles and their associated structures in patients with severe COPD. Methods Twelve medically stable patients (n=12) with an existing diagnosis of severe COPD (ten: GOLD Stage III and two: GOLD Stage IV) were included. Residual volume, inspiratory capacity and oxygen saturation (SpO2) were recorded immediately before and after administration of the STMTP. A Student’s t-test was used to determine the effect of the manual therapy intervention (P<0.05). Results The mean age of the patients was 62.4 years (range 46–77). Nine were male. Residual volume decreased from 4.5 to 3.9 L (P=0.002), inspiratory capacity increased from 2.0 to 2.1 L (P=0.039) and SpO2 increased from 93% to 96% (P=0.001). Conclusion A single application of an STMTP appears to have the potential to produce immediate clinically meaningful improvements in lung function in patients with severe and very severe COPD. PMID:28260875

Gene Therapy Targeting Glaucoma: Where Are We?

PubMed Central

Liu, Xuyang; Rasmussen, Carol A.; Gabelt, B’Ann T.; Brandt, Curtis R.; Kaufman, Paul L.

2010-01-01

In a chronic disease such as glaucoma, a therapy that provides a long lasting local effect, with minimal systemic side effects, while circumventing the issue of patient compliance, is very attractive. The field of gene therapy is growing rapidly and ocular applications are expanding. Our understanding of the molecular pathogenesis of glaucoma is leading to greater specificity in ocular tissue targeting. Improvements in gene delivery techniques, refinement of vector construction methods, and development of better animal models combine to bring this potential therapy closer to reality. PMID:19539835

[Low-energy wideband electromagnetic radiation and manual therapy in the treatment of neurological manifestations of spinal osteochondrosis].

PubMed

Afoshin, S A; Gerasimenko, M Iu

2006-01-01

It is shown that the advanced technique of low-energy wideband electromagnetic radiation improves vascular tonicity and peripheral circulation while a modified technique of manual therapy facilitates movements in the affected part of the spine and reduces tonicity of the muscles involved in the pathological process.

Management of pulmonary toxicity associated with targeted anticancer therapies.

PubMed

Teuwen, Laure-Anne; Van den Mooter, Tom; Dirix, Luc

2015-01-01

Targeted anticancer therapies act by interfering with defined molecular entities and/or biologic pathways. Because of their more specific mechanism of action, adverse events (AEs) on healthy tissues are intended to be minimal, resulting in a different toxicity profile from that observed with conventional cytotoxic chemotherapy. Pulmonary AEs are rare but potentially life-threatening and it is, therefore, critical to recognize early on and manage appropriately. In this review, we aim to offer an overview of both more frequent and rare pulmonary AEs caused by targeted anticancer therapies and discuss possible treatment algorithms. Anti-vascular endothelial growth factor, anti-human epidermal growth factor receptor and anti-CD20 therapy will be reviewed, as well as immune checkpoint inhibitors, anaplastic lymphoma kinase inhibitors and mammalian target of rapamycin inhibitors. Novel agents used in the treatment of cancer have specific side-effects, the result of allergic reactions, on-target and off-target effects. Clinical syndromes associated with pulmonary toxicity vary from bronchospasms, hypersensitivity reactions, pneumonitis, acute respiratory distress, lung bleeding, pleural effusion to pneumothorax. Knowledge of risk factors, a high index of suspicion and a complete diagnostic work-up are essential for limiting the risk of these events becoming life threatening. The development of treatment algorithms is extremely helpful in managing these events. It is probable that these toxicities will be even more frequent with the introduction of combination therapies with the obvious challenge of discerning the responsible agent.

Targeted therapy according to next generation sequencing-based panel sequencing.

PubMed

Saito, Motonobu; Momma, Tomoyuki; Kono, Koji

2018-04-17

Targeted therapy against actionable gene mutations shows a significantly higher response rate as well as longer survival compared to conventional chemotherapy, and has become a standard therapy for many cancers. Recent progress in next-generation sequencing (NGS) has enabled to identify huge number of genetic aberrations. Based on sequencing results, patients recommend to undergo targeted therapy or immunotherapy. In cases where there are no available approved drugs for the genetic mutations detected in the patients, it is recommended to be facilitate the registration for the clinical trials. For that purpose, a NGS-based sequencing panel that can simultaneously target multiple genes in a single investigation has been used in daily clinical practice. To date, various types of sequencing panels have been developed to investigate genetic aberrations with tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics. Because sequencing panels are efficient and cost-effective, they are quickly being adopted outside the lab, in hospitals and clinics, in order to identify personal targeted therapy for individual cancer patients.

New PARP targets for cancer therapy

PubMed Central

Vyas, Sejal; Chang, Paul

2015-01-01

Poly(ADP-ribose) polymerases (PARPs) modify target proteins post-translationally with poly(ADP-ribose) (PAR) or mono(ADP-ribose) (MAR) using NAD+ as substrate. The best-studied PARPs generate PAR modifications and include PARP1 and the tankyrase PARP5a, both of which are targets for cancer therapy with inhibitors in either clinical trials or preclinical development. There are 15 additional PARPs, the majority of which modify proteins with MAR, and their biology is less well understood. Recent data identify potentially cancer relevant functions for these PARPs, indicating that we need to understand more about these PARPs in order to target them effectively. PMID:24898058

Manual therapy and eccentric exercise in the management of Achilles tendinopathy.

PubMed

Jayaseelan, Dhinu J; Kecman, Michael; Alcorn, Daniel; Sault, Josiah D

2017-05-01

Chronic Achilles tendinopathy (AT) is an overuse condition seen among runners. Eccentric exercise can decrease pain and improve function for those with chronic degenerative tendon changes; however, some individuals have continued pain requiring additional intervention. While joint mobilization and manipulation has not been studied in the management in Achilles tendinopathy, other chronic tendon dysfunction, such as lateral epicondylalgia, has responded well to manual therapy (MT). Three runners were seen in physical therapy (PT) for chronic AT. They were prescribed eccentric loading exercises and calf stretching. Joint mobilization and manipulation was implemented to improve foot and ankle mobility, decrease pain, and improve function. Immediate within-session changes in pain, heel raise repetitions, and pressure pain thresholds (PPT) were noted following joint-directed MT in each patient. Each patient improved in self-reported function on the Achilles tendon specific Victorian Institute for Sport Assessment questionnaire (VISA-A), pain levels, PPT, joint mobility, ankle motion, and single-leg heel raises at discharge and 9-month follow-up. The addition of MT directed at local and remote sites may enhance the rehabilitation of patients with AT. Further research is necessary to determine the efficacy of adding joint mobilization to standard care for AT. Case series. Therapy, Level 4.

Enhancing Targeted Therapy for Myeloproliferative Neoplasms

DTIC Science & Technology

2013-10-01

Myeloproliferative Neoplasms PRINCIPAL INVESTIGATOR: Gary W. Reuther CONTRACTING...2. REPORT TYPE Annual 3. DATES COVERED 30 2012-2 2013 4. TITLE AND SUBTITLE Enhancing Targeted Therapy for Myeloproliferative Neoplasms ...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Myeloproliferative neoplasms

Familial breast cancer - targeted therapy in secondary and tertiary prevention.

PubMed

Kast, Karin; Rhiem, Kerstin

2015-02-01

The introduction of an increasing number of individualized molecular targeted therapies into clinical routine mirrors their importance in modern cancer prevention and treatment. Well-known examples for targeted agents are the monoclonal antibody trastuzumab and the selective estrogen receptor modulator tamoxifen. The identification of an unaltered gene in tumor tissue in colon cancer (KRAS) is a predictor for the patient's response to targeted therapy with a monoclonal antibody (cetuximab). Targeted therapy for hereditary breast and ovarian cancer has become a reality with the approval of olaparib for platin-sensitive late relapsed BRCA-associated ovarian cancer in December 2014. This manuscript reviews the status quo of poly-ADP-ribose polymerase inhibitors (PARPi) in the therapy of breast and ovarian cancer as well as the struggle for carboplatin as a potential standard of care for triple-negative and, in particular, BRCA-associated breast cancer. Details of the mechanism of action with information on tumor development are provided, and an outlook for further relevant research is given. The efficacy of agents against molecular targets together with the identification of an increasing number of cancer-associated genes will open the floodgates to a new era of treatment decision-making based on molecular tumor profiles. Current clinical trials involving patients with BRCA-associated cancer explore the efficacy of the molecular targeted therapeutics platinum and PARPi.

Trial Protocol: Cognitive functional therapy compared with combined manual therapy and motor control exercise for people with non-specific chronic low back pain: protocol for a randomised, controlled trial.

PubMed

Belache, Fabiana Terra Cunha; Souza, Cíntia Pereira de; Fernandez, Jessica; Castro, Julia; Ferreira, Paula Dos Santos; Rosa, Elizana Rodrigues de Sousa; Araújo, Nathalia Cristina Gimenez de; Reis, Felipe José Jandre; Almeida, Renato Santos de; Nogueira, Leandro Alberto Calazans; Correia, Luís Cláudio Lemos; Meziat-Filho, Ney

2018-06-11

Chronic low back pain is a public health problem, and there is strong evidence that it is associated with a complex interaction of biopsychosocial factors. Cognitive functional therapy is an intervention that deals with potentially modifiable multidimensional aspects of pain (eg, provocative cognitive, movement and lifestyle behaviours). There is evidence (from a single randomised, controlled trial) that cognitive functional therapy is better than combined manual therapy and motor control exercise. However, this study had significant methodological shortcomings including the failure to carry out an intention-to-treat analysis and a considerable loss of follow-up of participants. It is important to replicate this study in another domain through a randomised clinical trial with similar objectives but correcting these methodological shortcomings. To investigate the efficacy of cognitive functional therapy compared to combined manual therapy and exercise on pain and disability at 3 months in patients with chronic non-specific low back pain. Two-group, randomised, multicentre controlled trial with blinded assessors. One hundred and forty-eight participants with chronic low back pain that has persisted for >3months and no specific spinal pathology will be recruited from the school clinic of the Centro Universitário Augusto Motta and a private clinic in the city of Rio de Janeiro, Brazil. Four to 10 sessions of cognitive functional therapy. The physiotherapists who will treat the participants in the cognitive functional therapy group have previously attended 2 workshops with two different tutors of the method. Such physiotherapists have completed 106 hours of training, including workshops and patient examinations, as well as conducting a pilot study under the supervision of another physiotherapist with>3 years of clinical experience in cognitive functional therapy. Four to 10 sessions of combined manual therapy and motor control exercises. Participants in the combined

Targeted and Nontargeted α-Particle Therapies.

PubMed

McDevitt, Michael R; Sgouros, George; Sofou, Stavroula

2018-06-04

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease.

Targeted and Nontargeted α-Particle Therapies

PubMed Central

McDevitt, Michael R.; Sgouros, George; Sofou, Stavroula

2018-01-01

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease. PMID:29345977

The effects of sustained manual pressure stimulation according to Vojta Therapy on heart rate variability.

PubMed

Opavsky, Jaroslav; Slachtova, Martina; Kutin, Miroslav; Hok, Pavel; Uhlir, Petr; Opavska, Hana; Hlustik, Petr

2018-05-23

The physiotherapeutic technique of Vojta reflex locomotion is often accompanied by various autonomic activity changes and unpleasant sensations. It is unknown whether these effects are specific to Vojta Therapy. Therefore, the aim of this study was to compare changes in cardiac autonomic control after Vojta reflex locomotion stimulation and after an appropriate sham stimulation. A total of 28 young healthy adults (20.4 - 25.7 years) were enrolled in this single-blind randomized cross-over study. Participants underwent two modes of 20-minute sustained manual pressure stimulation on the surface of the foot on two separate visits. One mode used manual pressure on the lateral heel, i.e., in a zone employed in the Vojta Therapy (active stimulation). The other mode used pressure on the lateral ankle (control), in an area not included among the active zones used by Vojta Therapy and whose activation does not evoke manifestations of reflex locomotion. Autonomic nervous system activity was evaluated using spectral analysis of heart rate variability before and after the intervention. The active stimulation was perceived as more unpleasant than the control stimulation. Heart rate variability parameters demonstrated almost identical autonomic responses after both stimulation types, showing either modest increase in parasympathetic activity, or increased heart rate variability with similar contribution of parasympathetic and sympathetic activity. The results demonstrate changes of cardiac autonomic control in both active and control stimulation, without evidence for a significant difference between the two.

The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized clinical trial.

PubMed

Louw, Adriaan; Farrell, Kevin; Landers, Merrill; Barclay, Martin; Goodman, Elise; Gillund, Jordan; McCaffrey, Sara; Timmerman, Laura

2017-12-01

To determine if a neuroplasticity educational explanation for a manual therapy technique will produce a different outcome compared to a traditional mechanical explanation. Sixty-two patients with chronic low back pain (CLBP) were recruited for the study. Following consent, demographic data were obtained as well as pain ratings for low back pain (LBP) and leg pain (Numeric Pain Rating Scale), disability (Oswestry Disability Index), fear-avoidance (Fear-Avoidance-Beliefs Questionnaire), forward flexion (fingertips-to-floor), and straight leg raise (SLR) (inclinometer). Patients were then randomly allocated to receive one of two explanations (neuroplasticity or mechanical), a manual therapy technique to their lumbar spine, followed by post-intervention measurements of LBP, leg pain, forward flexion, and SLR. Sixty-two patients (female 35 [56.5%]), with a mean age of 60.1 years and mean duration of 9.26 years of CLBP participated in the study. There were no statistically significant interactions for LBP ( p  = .325), leg pain ( p  = .172), and trunk flexion ( p  = .818) between the groups, but SLR showed a significant difference in favor of the neuroplasticity explanation ( p  = .041). Additionally, the neuroplasticity group were 7.2 times (95% confidence interval = 1.8-28.6) more likely to improve beyond the MDC on the SLR than participants in the mechanical group. The results of this study show that a neuroplasticity explanation, compared to a traditional biomechanical explanation, resulted in a measureable difference in SLR in patients with CLBP when receiving manual therapy. Future studies need to explore if the increase in SLR correlated to changes in cortical maps of the low back.

Successes and limitations of targeted therapies in renal cell carcinoma.

PubMed

Pracht, Marc; Berthold, Dominik

2014-01-01

Until recently, the standard treatment for metastatic renal cell carcinoma (RCC) was nonspecific immunotherapy based on interleukin-2 or interferon-α. This was associated with a modest survival benefit and with significant clinical toxicities. The understanding of numerous molecular pathways in RCC, including HIF, VEGF, mTOR, and the consecutive use of targeted therapies since the beginning of 2005 have significantly improved outcomes for patients with metastatic RCC with an overall survival greater than 2 years. At present, at least 7 targeted agents are approved for first and consecutive lines of treatment of clear cell metastatic RCC. Long-term benefit and extended survival may be achieved through the optimal use of targeted therapies: optimal dosing, adverse event management and treatment duration and compliance. Advances in the finding of prognostic factors highlight the potential for personalizing treatment for patients with metastatic RCC. Data regarding the best sequencing of targeted therapies, predictive biomarkers, best timing of surgery, patient risk profiles, understanding of resistance mechanisms and safety of targeted therapies are growing and will provide a further step ahead in the management of advanced RCC. In parallel, a new class of therapeutics is emerging in RCC: immunotherapy; in particular check-point blockade antibodies are showing very promising results. © 2014 S. Karger AG, Basel.

Comparison of manual lymph drainage therapy and connective tissue massage in women with fibromyalgia: a randomized controlled trial.

PubMed

Ekici, Gamze; Bakar, Yesim; Akbayrak, Turkan; Yuksel, Inci

2009-02-01

This study analyzed and compared the effects of manual lymph drainage therapy (MLDT) and connective tissue massage (CTM) in women with primary fibromyalgia (PFM). The study design was a randomized controlled trial. Fifty women with PFM completed the study. The patients were divided randomly into 2 groups. Whereas 25 of them received MLDT, the other 25 underwent CTM. The treatment program was carried out 5 times a week for 3 weeks in each group. Pain was evaluated by a visual analogue scale and algometry. The Fibromyalgia Impact Questionnaire (FIQ) and Nottingham Health Profile were used to describe health status and health-related quality of life (HRQoL). Wilcoxon signed rank test and Mann-Whitney U test were used to analyze the data. In both groups, significant improvements were found regarding pain intensity, pain pressure threshold, and HRQoL (P < .05). However, the scores of FIQ-7 (P = .006), FIQ-9 (P = .006), and FIQ-total (P = .010) were significantly lower in the MLDT group than they were in the CTM group at the end of treatment. For this particular group of patients, both MLDT and CTM appear to yield improvements in terms of pain, health status, and HRQoL. The results indicate that these manual therapy techniques might be used in the treatment of PFM. However, MLDT was found to be more effective than CTM according to some subitems of FIQ (morning tiredness and anxiety) and FIQ total score. Manual lymph drainage therapy might be preferred; however, further long-term follow-up studies are needed.

Ottawa panel evidence-based clinical practice guidelines for therapeutic exercises and manual therapy in the management of osteoarthritis.

PubMed

2005-09-01

Osteoarthritis (OA) affects a large and growing proportion of the population. The purpose of this project was to create guidelines for the use of therapeutic exercises and manual therapy in the management of adult patients (>18 years of age) with a diagnosis of OA. All stages of the disease were included in the analysis, and studies of patients who had recent surgery or other rheumatologic, musculoskeletal, or spinal problems or of subjects without known pathology or impairments were excluded. The Ottawa Methods Group used Cochrane Collaboration methods to find and synthesize evidence from comparative controlled trials and then asked stakeholder groups to nominate representatives to serve on a panel of experts. The Ottawa Panel agreed on criteria for grading the strength of the recommendations and their supporting evidence. Of the 609 potential articles on therapeutic exercises for OA that were identified, 113 were considered potentially relevant, and 26 randomized controlled trials and controlled clinical trials were ultimately used. Sixteen positive recommendations of clinical benefit were developed for therapeutic exercises, especially strengthening exercises and general physical activity, particularly for the management of pain and improvement of functional status. Manual therapy combined with exercises also is recommended in the management of patients with OA. The Ottawa Panel recommends the use of therapeutic exercises alone, or combined with manual therapy, for managing patients with OA. There were a total of 16 positive recommendations: 13 grade A and 3 grade C+. The Ottawa Panel recommends the use of therapeutic exercises because of the strong evidence (grades A, B, and C+) in the literature.

Chronic lymphocytic leukemia therapy: new targeted therapies on the way

PubMed Central

Vitale, Candida; Burger, Jan A

2016-01-01

Introduction The critical role of the tissue microenvironment and B cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL) pathogenesis, and the clinical success of targeted agents that disrupt BCR signaling are currently changing the CLL landscape. Three new drugs were recently approved for CLL therapy, and other agents are in late development. Areas covered In this review, we summarize data on promising new targeted drugs for CLL. The heterogeneous mechanisms of actions of these molecules are described, such as the inhibition of BCR signaling, direct targeting of CD20 molecules on the CLL cell surface, and BCL-2 inhibition. We present preclinical and clinical data from phase I to III studies in order to describe efficacy and side effect profile of these new drugs. Data are derived from peer-reviewed articles indexed in PubMed and from abstracts presented at major international meetings. Expert opinion Ibrutinib and idelalisib are challenging the role of chemo-immunotherapy in CLL therapy in the frontline and relapsed disease settings. High-risk CLL patients particularly benefit from these new agents. Venetoclax and obinutuzumab are other effective agents added to our therapeutic armamentarium. Studies to better define the optimal use of these drugs, alone, or rather in combination or sequenced are underway. PMID:26988407

Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer.

PubMed

Janmaat, Vincent T; Steyerberg, Ewout W; van der Gaast, Ate; Mathijssen, Ron Hj; Bruno, Marco J; Peppelenbosch, Maikel P; Kuipers, Ernst J; Spaander, Manon Cw

2017-11-28

Almost half of people with esophageal or gastroesophageal junction cancer have metastatic disease at the time of diagnosis. Chemotherapy and targeted therapies are increasingly used with a palliative intent to control tumor growth, improve quality of life, and prolong survival. To date, and with the exception of ramucirumab, evidence for the efficacy of palliative treatments for esophageal and gastroesophageal cancer is lacking. To assess the effects of cytostatic or targeted therapy for treating esophageal or gastroesophageal junction cancer with palliative intent. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Web of Science, PubMed Publisher, Google Scholar, and trial registries up to 13 May 2015, and we handsearched the reference lists of studies. We did not restrict the search to publications in English. Additional searches were run in September 2017 prior to publication, and they are listed in the 'Studies awaiting assessment' section. We included randomized controlled trials (RCTs) on palliative chemotherapy and/or targeted therapy versus best supportive care or control in people with esophageal or gastroesophageal junction cancer. Two authors independently extracted data. We assessed the quality and risk of bias of eligible studies according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated pooled estimates of effect using an inverse variance random-effects model for meta-analysis. We identified 41 RCTs with 11,853 participants for inclusion in the review as well as 49 ongoing studies. For the main comparison of adding a cytostatic and/or targeted agent to a control arm, we included 11 studies with 1347 participants. This analysis demonstrated an increase in overall survival in favor of the arm with an additional cytostatic or targeted therapeutic agent with a hazard ratio (HR) of 0.75 (95% confidence interval (CI) 0.68 to 0.84, high-quality evidence). The median increased

A comparison of two manual physical therapy approaches and electrotherapy modalities for patients with knee osteoarthritis: A randomized three arm clinical trial.

PubMed

Kaya Mutlu, Ebru; Ercin, Ersin; Razak Ozdıncler, Arzu; Ones, Nadir

2018-08-01

A broad spectrum of physical therapy exercise programs provides symptom relief and functional benefit for patients with knee OA. Manual physical therapy, including tailored exercise programs provide relatively higher level benefit that persists to one year. It is currently unknown if there are important differences in the effects of different manual physical therapy techniques for patients with knee OA and there are virtually no studies comparing manual physical therapy and electrotherapy modalities. The aim of the study was to compare long-term results between three treatment groups (mobilization with movements [MWMs], passive joint mobilization [PJM], and electrotherapy) to determine which treatment is most effective in patients with knee OA. A single-blind randomized clinical trial with parallel design was conducted in patients with knee OA. Seventy-two consecutive patients (mean age 56.11 ± 6.80 years) with bilateral knee OA were randomly assigned to one of three treatment groups: MWMs, PJM, and electrotherapy. All groups performed an exercise program and received 12 sessions. The primary outcome measures of the functional assessment were the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and Aggregated Locomotor Function (ALF) test scores. The secondary outcome measures were pain level, measured using a pressure algometer and a visual analogue scale (VAS), range of motion (ROM), measured using a digital goniometer, and muscle strength, evaluated with a handheld dynamometer. Patients were assessed before treatment, after treatment and after 1 year of follow-up. Patients receiving the manual physical therapy interventions consisting of either MWM or PJM demonstrated a greater decrease in VAS scores at rest, during functional activities, and during the night compared to those in the electrotherapy group from baseline to after the treatment (p < 0.05). This improvement continued at the 1-year follow-up (p < 0.05). The MWMs and PJM

Cancer-targeted therapies and radiopharmaceuticals

PubMed Central

Rachner, Tilman D; Jakob, Franz; Hofbauer, Lorenz C

2015-01-01

The treatment of bone metastases remains a clinical challenge. Although a number of well-established agents, namely bisphosphonates and denosumab, are available to reduce the occurrence of skeletal-related events, additional cancer-targeted therapies are required to improve patients' prognosis and quality of life. This review focuses on novel targets and agents that are under clinical evaluation for the treatment of malignant bone diseases such as activin A, src and endothelin-1 inhibition or agents that are clinically approved and may positively influence bone, such as the mTOR inhibitor everolimus. In addition, the potential of alpharadin, a novel radiopharmaceutical approved for the treatment of prostatic bone disease, is discussed. PMID:26131359

Targeting RNA Splicing for Disease Therapy

PubMed Central

Havens, Mallory A.; Duelli, Dominik M.

2013-01-01

Splicing of pre-messenger RNA into mature messenger RNA is an essential step for expression of most genes in higher eukaryotes. Defects in this process typically affect cellular function and can have pathological consequences. Many human genetic diseases are caused by mutations that cause splicing defects. Furthermore, a number of diseases are associated with splicing defects that are not attributed to overt mutations. Targeting splicing directly to correct disease-associated aberrant splicing is a logical approach to therapy. Splicing is a favorable intervention point for disease therapeutics, because it is an early step in gene expression and does not alter the genome. Significant advances have been made in the development of approaches to manipulate splicing for therapy. Splicing can be manipulated with a number of tools including antisense oligonucleotides, modified small nuclear RNAs (snRNAs), trans-splicing, and small molecule compounds, all of which have been used to increase specific alternatively spliced isoforms or to correct aberrant gene expression resulting from gene mutations that alter splicing. Here we describe clinically relevant splicing defects in disease states, the current tools used to target and alter splicing, specific mutations and diseases that are being targeted using splice-modulating approaches, and emerging therapeutics. PMID:23512601

Targeting RNA splicing for disease therapy.

PubMed

Havens, Mallory A; Duelli, Dominik M; Hastings, Michelle L

2013-01-01

Splicing of pre-messenger RNA into mature messenger RNA is an essential step for the expression of most genes in higher eukaryotes. Defects in this process typically affect cellular function and can have pathological consequences. Many human genetic diseases are caused by mutations that cause splicing defects. Furthermore, a number of diseases are associated with splicing defects that are not attributed to overt mutations. Targeting splicing directly to correct disease-associated aberrant splicing is a logical approach to therapy. Splicing is a favorable intervention point for disease therapeutics, because it is an early step in gene expression and does not alter the genome. Significant advances have been made in the development of approaches to manipulate splicing for therapy. Splicing can be manipulated with a number of tools including antisense oligonucleotides, modified small nuclear RNAs (snRNAs), trans-splicing, and small molecule compounds, all of which have been used to increase specific alternatively spliced isoforms or to correct aberrant gene expression resulting from gene mutations that alter splicing. Here we describe clinically relevant splicing defects in disease states, the current tools used to target and alter splicing, specific mutations and diseases that are being targeted using splice-modulating approaches, and emerging therapeutics. Copyright © 2013 John Wiley & Sons, Ltd.

Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies

PubMed Central

Thaker, Nikhil G; Pollack, Ian F

2010-01-01

Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient’s tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG. PMID:19951140

The Brockport Physical Fitness Test Training Manual. [Project Target].

ERIC Educational Resources Information Center

Winnick, Joseph P.; Short, Francis X., Ed.

This training manual presents information on the Brockport Physical Fitness Test (BPFT), a criterion-referenced fitness test for children and adolescents with disabilities. The first chapter of the test training manual includes information dealing with health-related criterion-referenced testing, the interaction between physical activity and…

Targeted Therapy: Attacking Cancer with Molecular and Immunological Targeted Agents.

PubMed

Wilkes, Gail M

2018-01-01

Today, personalized cancer therapy with targeted agents has taken center stage, and offers individualized treatment to many. As the mysteries of the genes in a cell's DNA and their specific proteins are defined, advances in the understanding of cancer gene mutations and how cancer evades the immune system have been made. This article provides a basic and simplified understanding of the available (Food and Drug Administration- approved) molecularly and immunologically targeted agents in the USA. Other agents may be available in Asia, and throughout the USA and the world, many more agents are being studied. Nursing implications for drug classes are reviewed.

[Application of mechanical measurement in assessment of neck pain and manual therapy].

PubMed

Wang, Kuan; Deng, Zhen; Wang, Hui-Hao; Niu, Wen-Xin; Zhan, Hong-Sheng

2016-07-25

Manual therapy is one of the effective methods in treating neck pain. It has certain advantages in the short term to ease the symptoms of neck pain. In recent years, using different mechanical sensors and imaging equipment with computer software, the researchers found the difference of cervical activity between health adult and patients with neck pain. They also analyzed the kinematics, magnitude of force, stress and strain of the related structure and other mechanical parameters during cervical manipulation. These biomechanical researches revealed the functional anomaly caused by neck pain, reflect the safety of cervical manipulation, explain the abnormal stress of neck pain and the adjusting role of manipulation. Relatively speaking, these studies are too basic, and their analysis also are limited for the stress and strain about internal tissue. Study to aim directly at above problems will have important significance in understanding neck pain and standardizing manipulation therapy. Copyright© 2016 by the China Journal of Orthopaedics and Traumatology Press.

Personalized targeted therapy for esophageal squamous cell carcinoma

PubMed Central

Kang, Xiaozheng; Chen, Keneng; Li, Yicheng; Li, Jianying; D'Amico, Thomas A; Chen, Xiaoxin

2015-01-01

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial. PMID:26167067

Physical therapy treatment effectiveness for osteoarthritis of the knee: a randomized comparison of supervised clinical exercise and manual therapy procedures versus a home exercise program.

PubMed

Deyle, Gail D; Allison, Stephen C; Matekel, Robert L; Ryder, Michael G; Stang, John M; Gohdes, David D; Hutton, Jeremy P; Henderson, Nancy E; Garber, Matthew B

2005-12-01

Manual therapy and exercise have not previously been compared with a home exercise program for patients with osteoarthritis (OA) of the knee. The purpose of this study was to compare outcomes between a home-based physical therapy program and a clinically based physical therapy program. One hundred thirty-four subjects with OA of the knee were randomly assigned to a clinic treatment group (n=66; 61% female, 39% male; mean age [+/-SD]=64+/-10 years) or a home exercise group (n=68, 71% female, 29% male; mean age [+/-SD]=62+/-9 years). Subjects in the clinic treatment group received supervised exercise, individualized manual therapy, and a home exercise program over a 4-week period. Subjects in the home exercise group received the same home exercise program initially, reinforced at a clinic visit 2 weeks later. Measured outcomes were the distance walked in 6 minutes and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Both groups showed clinically and statistically significant improvements in 6-minute walk distances and WOMAC scores at 4 weeks; improvements were still evident in both groups at 8 weeks. By 4 weeks, WOMAC scores had improved by 52% in the clinic treatment group and by 26% in the home exercise group. Average 6-minute walk distances had improved about 10% in both groups. At 1 year, both groups were substantially and about equally improved over baseline measurements. Subjects in the clinic treatment group were less likely to be taking medications for their arthritis and were more satisfied with the overall outcome of their rehabilitative treatment compared with subjects in the home exercise group. Although both groups improved by 1 month, subjects in the clinic treatment group achieved about twice as much improvement in WOMAC scores than subjects who performed similar unsupervised exercises at home. Equivalent maintenance of improvements at 1 year was presumably due to both groups continuing the identical home exercise program

Tes, a potential Mena-related cancer therapy target.

PubMed

Li, X

2008-02-01

Cancer remains one of the world's most prominent causes of human morbidity and mortality, particularly in developing countries. According to 2005 statistics from the WHO, approximately 7.6 million people died of cancer out of 58 million deaths worldwide, with 9 million people estimated to die from cancer in 2015 and 11.4 million to die in 2030 (http://www.who.int/mediacentre/factsheets/fs297/en/index.html). The principal and internationally recognized methods of cancer treatment are surgery, radiotherapy, chemotherapy, or multimodality therapy. With the recent development of cancer biology, more and more tumor-related targets have been identified, ushering in a new era for target therapy. Every possible step that causes cellular cancer, such as signal transduction pathways, oncogenes and anti-oncogenes, cytokines and receptors, antiangiogenesis, suicide genes, and telomerase (Shay JW, Keith WN. Br J Cancer 2008), that is biologically relevant, reproducibly measurable, and definably correlated with clinical benefit represents a target for target therapies like targeting gene-virotherapy and monoclonal antibody-directed therapy. These therapies can specifically inhibit the growth of tumor cells at the molecular level and even kill them. Generally speaking, cancer-related targets should be crucial to the tumor's malignant phenotype, easily measurable in readily obtained clinical samples, and yield a significant clinical response. Since tumorigenesis is a very complex process involving the interaction of multiple factors and pathways, target treatment offers hopes to maximize efficacy while minimizing toxicity and specificity. More importantly, treatment should have little or no toxicity on normal cells, thus representing the most promising aspect of cancer research (Friday BB, Adjei AA. Clin Cancer Res 2008; 14:342-346). A recent cancer study has provided exciting information. According to Xinhua News from London, Michael Way and fellow researchers from Cancer

Development of targeted therapy and immunotherapy for treatment of small cell lung cancer.

PubMed

Saito, Motonobu; Shiraishi, Kouya; Goto, Akiteru; Suzuki, Hiroyuki; Kohno, Takashi; Kono, Koji

2018-05-14

Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC. Recent advances in the understanding of molecular biology have revealed several candidate therapeutic targets. To date, poly [ADP-ribose] polymerase (PARP), enhancer of zeste homologue 2 (EZH2) or delta-like canonical Notch ligand 3 (DLL3) are considered to be druggable targets in SCLC. In addition, another candidate of personalized therapy for SCLC is immune blockade therapy of programmed death-1 (PD-1) and its ligand, PD-L1. PD-1/PD-L1 blockade therapy is not a standard therapy for SCLC, so many clinical trials have been performed to investigate its efficacy. Herein, we review gene aberrations exploring the utility of targeted therapy and discuss blockade of immune checkpoints therapy in SCLC.

Targeted Therapies in Non-Small Cell Lung Cancer—Beyond EGFR and ALK

PubMed Central

Rothschild, Sacha I.

2015-01-01

Systemic therapy for non-small cell lung cancer (NSCLC) has undergone a dramatic paradigm shift over the past decade. Advances in our understanding of the underlying biology of NSCLC have revealed distinct molecular subtypes. A substantial proportion of NSCLC depends on oncogenic molecular aberrations (so-called “driver mutations”) for their malignant phenotype. Personalized therapy encompasses the strategy of matching these subtypes with effective targeted therapies. EGFR mutations and ALK translocation are the most effectively targeted oncogenes in NSCLC. EGFR mutations and ALK gene rearrangements are successfully being targeted with specific tyrosine kinase inhibitors. The number of molecular subgroups of NSCLC continues to grow. The scope of this review is to discuss recent data on novel molecular targets as ROS1, BRAF, KRAS, HER2, c-MET, RET, PIK3CA, FGFR1 and DDR2. Thereby the review will focus on therapeutic strategies targeting these aberrations. Moreover, the emerging challenge of acquired resistance to initially effective therapies will be discussed. PMID:26018876

Targeted Therapies in Non-Small Cell Lung Cancer-Beyond EGFR and ALK.

PubMed

Rothschild, Sacha I

2015-05-26

Systemic therapy for non-small cell lung cancer (NSCLC) has undergone a dramatic paradigm shift over the past decade. Advances in our understanding of the underlying biology of NSCLC have revealed distinct molecular subtypes. A substantial proportion of NSCLC depends on oncogenic molecular aberrations (so-called "driver mutations") for their malignant phenotype. Personalized therapy encompasses the strategy of matching these subtypes with effective targeted therapies. EGFR mutations and ALK translocation are the most effectively targeted oncogenes in NSCLC. EGFR mutations and ALK gene rearrangements are successfully being targeted with specific tyrosine kinase inhibitors. The number of molecular subgroups of NSCLC continues to grow. The scope of this review is to discuss recent data on novel molecular targets as ROS1, BRAF, KRAS, HER2, c-MET, RET, PIK3CA, FGFR1 and DDR2. Thereby the review will focus on therapeutic strategies targeting these aberrations. Moreover, the emerging challenge of acquired resistance to initially effective therapies will be discussed.

Manual Physical Therapy for Non-Surgical Treatment of Adhesion-Related Small Bowel Obstructions: Two Case Reports

PubMed Central

Rice, Amanda D.; King, Richard; Reed, Evette D’Avy; Patterson, Kimberley; Wurn, Belinda F.; Wurn, Lawrence J.

2013-01-01

Background: Adhesion formation is a widely acknowledged risk following abdominal or pelvic surgery. Adhesions in the abdomen or pelvis can cause or contribute to partial or total small bowel obstruction (SBO). These adhesions deter or prevent the passage of nutrients through the digestive tract, and may bind the bowel to the peritoneum, or other organs. Small bowel obstructions can quickly become life-threatening, requiring immediate surgery to resect the bowel, or lyse any adhesions the surgeon can safely access. Bowel repair is an invasive surgery, with risks including bowel rupture, infection, and peritonitis. An additional risk includes the formation of new adhesions during the healing process, creating the potential for subsequent adhesiolysis or SBO surgeries. Objective: Report the use of manual soft tissue physical therapy for the reversal of adhesion-related partial SBOs, and create an initial inquiry into the possibility of nonsurgical lysis of adhesions. Case Reports: Two patients presenting with SBO symptoms due to abdominal adhesions secondary to abdominal and pelvic surgery were treated with manual soft tissue physical therapy focused on decreasing adhesions. Conclusions: Successful treatment with resolution of symptom presentation of partial SBO and sustained results were observed in both patients treated. PMID:26237678

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

PubMed

Peng, Le; Zhang, Chao; Zhou, Lan; Zuo, Hong-Xia; He, Xiao-Kuo; Niu, Yu-Ming

2018-04-01

To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I 2  = 71%, P = 0.0005). Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

PubMed Central

Zhou, Jiehua; Rossi, John J.

2014-01-01

One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges. PMID:24936916

Application of stem cells in targeted therapy of breast cancer: a systematic review.

PubMed

Madjd, Zahra; Gheytanchi, Elmira; Erfani, Elham; Asadi-Lari, Mohsen

2013-01-01

The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. A systematic literature search was performed for original articles published from January 2007 until May 2012. Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. Wnt/β-catenin signaling pathway has been also evidenced to be an attractive CSC-target. This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

Targeted Therapy: Attacking Cancer with Molecular and Immunological Targeted Agents

PubMed Central

Wilkes, Gail M.

2018-01-01

Today, personalized cancer therapy with targeted agents has taken center stage, and offers individualized treatment to many. As the mysteries of the genes in a cell's DNA and their specific proteins are defined, advances in the understanding of cancer gene mutations and how cancer evades the immune system have been made. This article provides a basic and simplified understanding of the available (Food and Drug Administration- approved) molecularly and immunologically targeted agents in the USA. Other agents may be available in Asia, and throughout the USA and the world, many more agents are being studied. Nursing implications for drug classes are reviewed. PMID:29607374

Targeting neutrophils for host-directed therapy to treat tuberculosis.

PubMed

Dallenga, Tobias; Linnemann, Lara; Paudyal, Bhesh; Repnik, Urska; Griffiths, Gareth; Schaible, Ulrich E

2017-10-07

M. tuberculosis is one of the prime killers from infectious diseases worldwide. Infections with multidrug-resistant variants counting for almost half a million new cases per year are steadily on the rise. Tuberculosis caused by extensively drug-resistant variants that are even resistant against newly developed or last resort antibiotics have to be considered untreaTable Susceptible tuberculosis already requires a six-months combinational therapy which requires further prolongation to treat drug-resistant infections. Such long treatment schedules are often accompanied by serious adverse effects causing patients to stop therapy. To tackle the global tuberculosis emergency, novel approaches for treatment need to be urgently explored. Host-directed therapies that target components of the defense system represent such a novel approach. In this review, we put a spotlight on neutrophils and neutrophil-associated effectors as promising targets for adjunct host-directed therapies to improve antibiotic efficacy and reduce both, treatment time and long-term pathological sequelae. Copyright © 2017 Elsevier GmbH. All rights reserved.

Manual for Transference Work Scale; a micro-analytical tool for therapy process analyses.

PubMed

Ulberg, Randi; Amlo, Svein; Høglend, Per

2014-11-18

The present paper is a manual for the Transference Work Scale (TWS). The inter-rater agreement on the 26 TWS items was good to excellent and previously published. TWS is a therapy process rating scale focusing on Transference Work (TW) (i.e. analysis of the patient-therapist relationship). TW is considered a core active ingredient in dynamic psychotherapy. Adequate process scales are needed to identify and analyze in-session effects of therapist techniques in psychodynamic psychotherapy and empirically establish their links to outcome. TWS was constructed to identify and categorize relational (transference) interventions, and explore the in-session impact of analysis of the patient-therapist relationship (transference work). TWS has sub scales that rate timing, content, and valence of the transference interventions, as well as response from the patient. Descriptions and elaborations of the items in TWS are provided. Clinical examples of transference work from the First Experimental Study of Transference Interpretations (FEST) are included and followed by examples of how to rate transcripts from therapy sessions with TWS. The present manual describes in detail the rating procedure when using Transference Work Scale. Ratings are illustrated with clinical examples from FEST. TWS might be a potentially useful tool to explore the interaction of timing, category, and valence of transference work in predicting in-session patient response as well as treatment outcome. TWS might prove especially suitable for intensive case studies combining quantitative and narrative data. First Experimental Study of Transference-interpretations (FEST307/95). ClinicalTrials.gov Identifier: NCT00423462. URL: http://clinicaltrials.gov/ct2/show/NCT00423462?term=FEST&rank=2.

Review of the current targeted therapies for non-small-cell lung cancer

PubMed Central

Nguyen, Kim-Son H; Neal, Joel W; Wakelee, Heather

2014-01-01

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790M-targeted agents CO-1686 and AZD9291, and the ALK-targeted agents ceritinib (LDK378), AP26113, alectinib (CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come. PMID:25302162

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.

Bacteriophages and medical oncology: targeted gene therapy of cancer.

PubMed

Bakhshinejad, Babak; Karimi, Marzieh; Sadeghizadeh, Majid

2014-08-01

Targeted gene therapy of cancer is of paramount importance in medical oncology. Bacteriophages, viruses that specifically infect bacterial cells, offer a variety of potential applications in biomedicine. Their genetic flexibility to go under a variety of surface modifications serves as a basis for phage display methodology. These surface manipulations allow bacteriophages to be exploited for targeted delivery of therapeutic genes. Moreover, the excellent safety profile of these viruses paves the way for their potential use as cancer gene therapy platforms. The merge of phage display and combinatorial technology has led to the emergence of phage libraries turning phage display into a high throughput technology. Random peptide libraries, as one of the most frequently used phage libraries, provide a rich source of clinically useful peptide ligands. Peptides are known as a promising category of pharmaceutical agents in medical oncology that present advantages such as inexpensive synthesis, efficient tissue penetration and the lack of immunogenicity. Phage peptide libraries can be screened, through biopanning, against various targets including cancer cells and tissues that results in obtaining cancer-homing ligands. Cancer-specific peptides isolated from phage libraries show huge promise to be utilized for targeting of various gene therapy vectors towards malignant cells. Beyond doubt, bacteriophages will play a more impressive role in the future of medical oncology.

Targeting gene therapy to cancer: a review.

PubMed

Dachs, G U; Dougherty, G J; Stratford, I J; Chaplin, D J

1997-01-01

In recent years the idea of using gene therapy as a modality in the treatment of diseases other than genetically inherited, monogenic disorders has taken root. This is particularly obvious in the field of oncology where currently more than 100 clinical trials have been approved worldwide. This report will summarize some of the exciting progress that has recently been made with respect to both targeting the delivery of potentially therapeutic genes to tumor sites and regulating their expression within the tumor microenvironment. In order to specifically target malignant cells while at the same time sparing normal tissue, cancer gene therapy will need to combine highly selective gene delivery with highly specific gene expression, specific gene product activity, and, possibly, specific drug activation. Although the efficient delivery of DNA to tumor sites remains a formidable task, progress has been made in recent years using both viral (retrovirus, adenovirus, adeno-associated virus) and nonviral (liposomes, gene gun, injection) methods. In this report emphasis will be placed on targeted rather than high-efficiency delivery, although those would need to be combined in the future for effective therapy. To date delivery has been targeted to tumor-specific and tissue-specific antigens, such as epithelial growth factor receptor, c-kit receptor, and folate receptor, and these will be described in some detail. To increase specificity and safety of gene therapy further, the expression of the therapeutic gene needs to be tightly controlled within the target tissue. Targeted gene expression has been analyzed using tissue-specific promoters (breast-, prostate-, and melanoma-specific promoters) and disease-specific promoters (carcinoembryonic antigen, HER-2/neu, Myc-Max response elements, DF3/MUC). Alternatively, expression could be regulated externally with the use of radiation-induced promoters or tetracycline-responsive elements. Another novel possibility that will be

Practical issues of biomarker-assisted targeted therapy in precision medicine and immuno-oncology era.

PubMed

Lee, Dae Ho

2018-01-01

The concept of precision medicine is not new, as multiplex and very sensitive methods, or next-generation sequencing and matched targeted cancer therapies, have come to clinical practice. Substantial progress has been made from the discovery to the development and clinical application of biomarkers and matched targeted therapies. However, there still remain many challenges and issues to be overcome in each step, from acquisition of tumour tissues through validation of biomarkers to the final decision on targeted therapy. This review will briefly touch on these issues, hoping to provide a better understanding and application of targeted therapy in cancer treatment in the era of precision medicine and immuno-oncology. It also helps to understand that the meaning or value of biomarker(s) and matched targeted therapy changes along with expansion of knowledge and advance of methodology, and constant efforts have to be made in evaluating the meaning and clinical value during the development and after the establishment of biomarkers or the approval of matched targeted therapies, which might be more complicated by the advent of new therapeutic agents and new diagnostic methods.

The effectiveness of manual therapy for the management of musculoskeletal disorders of the upper and lower extremities: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

PubMed

Southerst, Danielle; Yu, Hainan; Randhawa, Kristi; Côté, Pierre; D'Angelo, Kevin; Shearer, Heather M; Wong, Jessica J; Sutton, Deborah; Varatharajan, Sharanya; Goldgrub, Rachel; Dion, Sarah; Cox, Jocelyn; Menta, Roger; Brown, Courtney K; Stern, Paula J; Stupar, Maja; Carroll, Linda J; Taylor-Vaisey, Anne

2015-01-01

Musculoskeletal disorders (MSDs) of the upper and lower extremities are common in the general population and place a significant burden on the health care system. Manual therapy is recommended by clinical practice guidelines for the management of these injuries; however, there is limited evidence to support its effectiveness. The purpose of our review was to investigate the effectiveness of manual therapy in adults or children with MSDs of the upper or lower extremity. Randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effectiveness of manual therapy were eligible. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Paired reviewers screened studies for relevance and critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with low risk of bias were synthesized following best-evidence synthesis principles. Where available, we computed mean changes between groups, relative risks and 95 % CI. We screened 6047 articles. Seven RCTs were critically appraised and three had low risk of bias. For adults with nonspecific shoulder pain of variable duration, cervicothoracic spinal manipulation and mobilization in addition to usual care may improve self-perceived recovery compared to usual care alone. For adults with subacromial impingement syndrome of variable duration, neck mobilization in addition to a multimodal shoulder program of care provides no added benefit. Finally, for adults with grade I-II ankle sprains of variable duration, lower extremity mobilization in addition to home exercise and advice provides greater short-term improvements in activities and function over home exercise and advice alone. No studies were included that evaluated the effectiveness of manual therapy in children or for the management of other extremity injuries in adults. The current evidence on the effectiveness of manual therapy

Advances in targeted therapy for acute myeloid leukaemia.

PubMed

Kayser, Sabine; Levis, Mark J

2018-02-01

In the past few years, research in the underlying pathogenic mechanisms of acute myeloid leukaemia (AML) has led to remarkable advances in our understanding of the disease. Cytogenetic and molecular aberrations are the most important factors in determining response to chemotherapy as well as long-term outcome, but beyond prognostication are potential therapeutic targets. Our increased understanding of the pathogenesis of AML, facilitated by next-generation sequencing, has spurred the development of new compounds in the treatment of AML, particularly the creation of small molecules that target the disease on a molecular level. Various new agents, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, monoclonal or bispecific T-cell engager antibodies, metabolic and pro-apoptotic agents are currently investigated within clinical trials. The highest response rates are often achieved when new molecularly targeted therapies are combined with standard chemotherapy. Presented here is an overview of novel therapies currently being evaluated in AML. © 2017 John Wiley & Sons Ltd.

Folate-targeted nanoparticles for rheumatoid arthritis therapy.

PubMed

Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

2016-05-01

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes

PubMed Central

Leclerc, Julie B.; O’Connor, Kieron P.; J.-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E.

2016-01-01

Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8–12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive–behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12–14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically. PMID:27563292

The Effect of a New Therapy for Children with Tics Targeting Underlying Cognitive, Behavioral, and Physiological Processes.

PubMed

Leclerc, Julie B; O'Connor, Kieron P; J-Nolin, Gabrielle; Valois, Philippe; Lavoie, Marc E

2016-01-01

Tourette disorder (TD) is characterized by motor and vocal tics, and children with TD tend to present a lower quality of life than neurotypical children. This study applied a manualized treatment for childhood tics disorder, Facotik, to a consecutive case series of children aged 8-12 years. The Facotik therapy was adapted from the adult cognitive and psychophysiological program validated on a range of subtypes of tics. This approach aims to modify the cognitive-behavioral and physiological processes against which the tic occurs, rather than only addressing the tic behavior. The Facotik therapy lasted 12-14 weeks. Each week 90-min session contained 20 min of parental training. The therapy for children followed 10 stages including: awareness training; improving motor control; modifying style of planning; cognitive and behavioral restructuring; and relapse prevention. Thirteen children were recruited as consecutive referrals from the general population, and seven cases completed therapy and posttreatment measures. Overall results showed a significant decrease in symptom severity as measured by the YGTSS and the TSGS. However, there was a discrepancy between parent and child rating, with some children perceiving an increase in tics, possibly due to improvement of awareness along therapy. They were also individual changes on adaptive aspects of behavior as measured with the BASC-2, and there was variability among children. All children maintained or improved self-esteem posttreatment. The results confirm the conclusion of a previous pilot study, which contributed to the adaptation of the adult therapy. In summary, the Facotik therapy reduced tics in children. These results underline that addressing processes underlying tics may complement approaches that target tics specifically.

Virus-Based Cancer Therapeutics for Targeted Photodynamic Therapy.

PubMed

Cao, Binrui; Xu, Hong; Yang, Mingying; Mao, Chuanbin

2018-01-01

Cancer photodynamic therapy (PDT) involves the absorption of light by photosensitizers (PSs) to generate cytotoxic singlet oxygen for killing cancer cells. The success of this method is usually limited by the lack of selective accumulation of the PS at cancer cells. Bioengineered viruses with cancer cell-targeting peptides fused on their surfaces are great drug carriers that can guide the PS to cancer cells for targeted cancer treatment. Here, we use cell-targeting fd bacteriophages (phages) as an example to describe how to chemically conjugate PSs (e.g., pyropheophorbide-a (PPa)) onto a phage particle to achieve targeted PDT.

Emission of Biophotons and Adjustable Sounds by the Fascial System: Review and Reflections for Manual Therapy.

PubMed

Bordoni, Bruno; Marelli, Fabiola; Morabito, Bruno; Sacconi, Beatrice

2018-01-01

Every body structure is wrapped in connective tissue or fascia, creating a structural continuity that gives form and function to every tissue and organ. The fascial tissue is uniformly distributed throughout the body, enveloping, interacting with and permeating blood vessels, nerves, viscera, meninges, bones and muscles, creating various layers at different depths and forming a tridimensional metabolic and mechanical matrix. This article reviews the literature on the emission of biophotons and adjustable sounds by the fascial system, because these biological changes could be a means of local and systemic cellular communication and become another assessment tool for manual (therapy) practitioners. This is the first article that discusses these topics in a single text, attempting to bring such information into an area of application that is beneficial to osteopaths, chiropractors, and manual therapists.

Emission of Biophotons and Adjustable Sounds by the Fascial System: Review and Reflections for Manual Therapy

PubMed Central

Marelli, Fabiola; Sacconi, Beatrice

2018-01-01

Every body structure is wrapped in connective tissue or fascia, creating a structural continuity that gives form and function to every tissue and organ. The fascial tissue is uniformly distributed throughout the body, enveloping, interacting with and permeating blood vessels, nerves, viscera, meninges, bones and muscles, creating various layers at different depths and forming a tridimensional metabolic and mechanical matrix. This article reviews the literature on the emission of biophotons and adjustable sounds by the fascial system, because these biological changes could be a means of local and systemic cellular communication and become another assessment tool for manual (therapy) practitioners. This is the first article that discusses these topics in a single text, attempting to bring such information into an area of application that is beneficial to osteopaths, chiropractors, and manual therapists. PMID:29405763

Dilemma-focused intervention for unipolar depression: a treatment manual.

PubMed

Feixas, Guillem; Compañ, Victoria

2016-07-12

This article introduces a new treatment protocol for depression. Based on previous research which indicated the presence of cognitive conflicts in depression, this study created an intervention manual to address these conflicts. The therapy manual for depressive patients followed the guideline for inclusion in clinical trials (stage II), which has received high recognition. A preliminary version (stage I) of this manual was formulated based on other, more general dilemma-focused therapy publications, inspired by personal construct theory (PCT), and input from clinical experience. The resulting version was then applied during the 8-session format of a pilot study with patients diagnosed with major depressive disorder or dysthymia. Finally, feedback was requested from seasoned and highly respected therapists, some of whom were familiar with PCT. According to the mentioned guideline, the intervention manual selected the theoretical framework, in this case PCT, to include its conceptualization of depression and resolution of dilemmas (to foster clinical improvement) as a main treatment goal. The manual was then contrasted with psychoanalytic psychotherapy, cognitive-behavior therapy (CBT), motivational interviewing (MI), and other similar approaches such as cognitive-analytic therapy and coherence therapy. Following these conceptual clarifications, the specific interventions included in the manual were defined according to both categories: their unique and essential components and those conceived as common psychotherapeutic factors. Next, the general structure and content for each session were presented. The structure consisted of seven well-defined individual sessions with an additional session, which could complement any of the former sessions to address the patient's issues in greater depth, if needed. This Dilemma-Focused Intervention manual aimed to improve the treatment outcome for depression by offering an intervention that could be combined with other general

Targeted therapy using nanotechnology: focus on cancer

PubMed Central

Sanna, Vanna; Pala, Nicolino; Sechi, Mario

2014-01-01

Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication. PMID:24531078

Manualized cognitive therapy versus cognitive-behavioral treatment-as-usual for social anxiety disorder in routine practice: A cluster-randomized controlled trial.

PubMed

Hoyer, Jürgen; Čolić, Jasmin; Pittig, Andre; Crawcour, Stephen; Moeser, Manuela; Ginzburg, Denise; Lin, Jihong; Wiltink, Joerg; Leibing, Eric; Stangier, Ulrich

2017-08-01

This study examined the effectiveness of manualized cognitive therapy (mCT) following the Clark-Wells approach versus non-manualized cognitive-behavioral treatment-as-usual (CBTAU) for social anxiety disorder (SAD) in routine practice. Forty-eight private practitioners were recruited within a multi-center trial and either received training in manualized CT for SAD or no such training. Practitioners treated 162 patients with SAD in routine practice (N = 107 completers, n = 57 for mCT, n = 50 for CBTAU). Social anxiety symptoms (Liebowitz Social Anxiety Scale; LSAS) and secondary measures were assessed before treatment, at treatment-hour 8, 15, and 25, at end of treatment, as well as 6 and 12 months after treatment. Patients in both groups showed significant reductions of SAD severity after treatment (d = 1.91 [mCT] and d = 1.80 [CBTAU], within-group effect sizes, intent-to-treat analyses, LSAS observer ratings), which remained stable at follow-up. There were no differences between groups in terms of symptom reduction and treatment duration. The present trial confirms the high effectiveness of CBTAU and mCT for SAD when practitioners conduct the treatments in routine practice. Additional training in the CT manual did not result in significant between-group effects on therapy outcome. Explanations for this unexpected result are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Organizational Effectiveness Case Development Manual

DTIC Science & Technology

1980-10-01

Target audience Legal issues UAmographic information Sanctions Write-up format L eaching case Pay-off s The manual is a guide for developing...most efficient and effective way. The manual is divided into three main sections: (1) on the issues of client system sanction, confidentiality, and...CASE DEVELOPMENT MANUAL James Bedoian, Larry E. Greiner, Charles P. Schaefer, Warren H. Schmidt, Stanley R. Weingart System Development Corporation

Targeted Drug and Gene Delivery Systems for Lung Cancer Therapy

PubMed Central

Sundaram, Sneha; Trivedi, Ruchit; Durairaj, Chandrasekar; Ramesh, Rajagopal; Ambati, Balamurali K.; Kompella, Uday B.

2009-01-01

Purpose To evaluate the efficacy of a novel docetaxel derivative of deslorelin, a luteinizing hormone releasing hormone (LHRH) agonist, and its combination in-vivo with RGD peptide conjugated nanoparticles encapsulating an anti-angiogenic, anti-VEGF intraceptor (Flt23k) (RGD-Flt23k-NP) in H1299 lung cancer cells and/or xenografts in athymic nude BALB/c mice. Experimental Design The in-vitro and in-vivo efficacy of the deslorelin-docetaxel conjugate (D-D) was evaluated in H1299 cells and xenografts in athymic nude mice. Co-administration of D-D and RGD-Flt23k-NP was tested in-vivo in mice. Tumor inhibition, apoptosis and VEGF inhibition were estimated in each of the treatment groups. Results The conjugate enhanced in-vitro docetaxel efficacy by 13-fold in H1299 cells compared to docetaxel at 24h, and this effect was inhibited following reduction of LHRH-receptor expression by an antisense oligonucleotide. Combination of the conjugate with the RGD-Flt23k-NP in-vivo resulted in an 82- and 15-fold tumor growth inhibition on day 39 following repeated weekly intravenous injections and a single intratumoral injection, respectively. These effects were significantly greater than individual targeted therapies or docetaxel alone. Similarly, apoptotic indices for the combination therapy were 14 and 10% in the intravenous and intratumoral groups, respectively, and higher than the individual therapies. Combination therapy groups exhibited greater VEGF inhibition in both the intravenous and intratumoral groups. Conclusions Docetaxel efficacy was enhanced by LHRH-receptor targeted deslorelin conjugate and further improved by combination with targeted anti-angiogenic nanoparticle gene therapy. Combination of novel targeted therapeutic approaches described here provides an attractive alternative to the current treatment options for lung cancer therapy. PMID:19920099

A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy.

PubMed

Mou, Quanbing; Ma, Yuan; Zhu, Xinyuan; Yan, Deyue

2016-05-28

Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Current therapies and targets for type 2 diabetes mellitus: a review.

PubMed

Chellapan, Dinesh K; Sheng Yap, Wei; Bt Ahmad Suhaimi, Nurfatihah A; Gupta, Gaurav; Dua, Kamal

2018-04-24

The prevalence of type 2 diabetes mellitus (T2DM) has been increasing at an alarming rate. With an increased understanding of the pathophysiology and pathogenesis of T2DM, various new therapeutic options have been developed to target different key defects in T2DM. Incremental innovations of existing therapies either through unprecedented drug combinations, modified drug molecules, or improved delivery systems are capable to nullify some of the undesirable side effects of traditional therapies as well as to enhance effectiveness. The existing administration routes include inhalation, nasal, buccal, parenteral and oral. Newer drug targets such as protein kinase B (Akt/PKB), AMPactivated protein kinase (AMPK), sirtuin (SIRT), and others are novel approaches that act via different mechanisms and possibly treating T2DM of distinct variations and aetiologies. Other therapies such as endobarrier, gene therapy, and stem cell technology utilize advanced techniques to treat T2DM, and the potential of these therapies are still being explored. Gene therapy is plausible to fix the underlying pathology of T2DM instead of using traditional reactive treatments, especially with the debut of Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR associated protein9 (CRISPRCas9) gene editing tool. Molecular targets in T2DM are also being extensively studied as it could target the defects at the molecular level. Furthermore, antibody therapies and vaccinations are also being developed against T2DM; but the ongoing clinical trials are relatively lesser and the developmental progress is slower. Although, there are many therapies designed to cure T2DM, each of them has their own advantages and disadvantages. The preference for the treatment plan usually depends on the health status of the patient and the treatment goal. Therefore, an ideal treatment should take patient's compliance, efficacy, potency, bioavailability, and other pharmacological and nonpharmacological properties

The roles of pathology in targeted therapy of women with gynecologic cancers.

PubMed

Murali, Rajmohan; Grisham, Rachel N; Soslow, Robert A

2018-01-01

The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor. Therefore, expanding the arsenal of available systemic therapies with targeted therapeutic agents is appealing. Anti-angiogenic therapies, immunotherapy and poly ADP ribose polymerase (PARP) inhibitors are now routinely used for the treatment of advanced gynecologic cancer, and many more are under investigation. Pathologists remain important in the clinical management of patients with targeted therapy, by identifying potentially targetable tumors on the basis of their pathologic phenotype, by assessing biomarkers that are predictive of response to targeted therapy (e.g. microsatellite instability, PD1/PDL1 expression), and by monitoring treatment response and resistance. Pathologists are also vital to research efforts exploring novel targeted therapies by identifying homogenous subsets of tumors for more reliable and meaningful analyses, and by confirming expression in tumor tissues of novel targets identified in genomic, epigenetic or other screening studies. In the era of precision gynecologic oncology, the roles of pathologists in the discovery, development and implementation of targeted therapeutic strategies remain as central as they are for traditional (surgery-chemotherapy-radiotherapy) management of women with gynecologic cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

New Molecular Targets of Anticancer Therapy - Current Status and Perspectives.

PubMed

Zajac, Marianna; Muszalska, Izabela; Jelinska, Anna

2016-01-01

Molecularly targeted anticancer therapy involves the use of drugs or other substances affecting specific molecular targets that play a part in the development, progression and spread of a given neoplasm. By contrast, the majority of classical chemotherapeutics act on all rapidly proliferating cells, both healthy and cancerous ones. Target anticancer drugs are designed to achieve a particular aim and they usually act cytostatically, not cytotoxically like classical chemotherapeutics. At present, more than 300 biological molecular targets have been identified. The proteins involved in cellular metabolism include (among others) receptor proteins, signal transduction proteins, mRNA thread matrix synthesis proteins participating in neoplastic transformation, cell cycle control proteins, functional and structural proteins. The receptor proteins that are targeted by currently used anticancer drugs comprise the epithelial growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor(VEGFR). Target anticancer drugs may affect extracellular receptor domains (antibodies) or intracellular receptor domains (tyrosine kinase inhibitors). The blocking of the mRNA thread containing information about the structure of oncogenes (signal transduction proteins) is another molecular target of anticancer drugs. That type of treatment, referred to as antisense therapy, is in clinical trials. When the synthesis of genetic material is disturbed, in most cases the passage to the next cycle phase is blocked. The key proteins responsible for the blockage are cyclines and cycline- dependent kinases (CDK). Clinical trials are focused on natural and synthetic substances capable of blocking various CDKs. The paper discusses the molecular targets and chemical structure of target anticancer drugs that have been approved for and currently applied in antineoplastic therapy together with indications and contraindications for their

Financial relationships in economic analyses of targeted therapies in oncology.

PubMed

Valachis, Antonis; Polyzos, Nikolaos P; Nearchou, Andreas; Lind, Pehr; Mauri, Davide

2012-04-20

A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.

Manual for Training Leprosy Rehabilitation Workers.

ERIC Educational Resources Information Center

Itoh, Masayoshi; Eason, Alice L.

The purpose of this manual is to introduce the general concepts and techniques in leprosy rehabilitation to physical therapy aides. Because of the lack of well-trained, qualified, physical therapists, the committee on leprosy rehabilitation considers it necessary to publish a teaching manual outlining leprosy rehabilitation for those who work with…

A cMUT probe for ultrasound-guided focused ultrasound targeted therapy.

PubMed

Gross, Dominique; Coutier, Caroline; Legros, Mathieu; Bouakaz, Ayache; Certon, Dominique

2015-06-01

Ultrasound-mediated targeted therapy represents a promising strategy in the arsenal of modern therapy. Capacitive micromachined ultrasonic transducer (cMUT) technology could overcome some difficulties encountered by traditional piezoelectric transducers. In this study, we report on the design, fabrication, and characterization of an ultrasound-guided focused ultrasound (USgFUS) cMUT probe dedicated to preclinical evaluation of targeted therapy (hyperthermia, thermosensitive liposomes activation, and sonoporation) at low frequency (1 MHz) with simultaneous ultrasonic imaging and guidance (15 to 20 MHz). The probe embeds two types of cMUT arrays to perform the modalities of targeted therapy and imaging respectively. The wafer-bonding process flow employed for the manufacturing of the cMUTs is reported. One of its main features is the possibility of implementing two different gap heights on the same wafer. All the design and characterization steps of the devices are described and discussed, starting from the array design up to the first in vitro measurements: optical (microscopy) and electrical (impedance) measurements, arrays' electroacoustic responses, focused pressure field mapping (maximum peak-to-peak pressure = 2.5 MPa), and the first B-scan image of a wire-target phantom.

A manual-based psychodynamic therapy for treatment-resistant borderline personality disorder.

PubMed

Gregory, Robert J; Remen, Anna L

2008-03-01

The authors introduce a manual-based treatment, labeled dynamic deconstructive psychotherapy, developed for those patients with borderline personality disorder who are most difficult to engage in therapy, such as those having co-occurring substance use disorders. This treatment model is based on the hypothesis that borderline pathology and related behaviors reflect impairment in specific neurocognitive functions, including association, attribution, and alterity that form the basis for a coherent and differentiated self. Dynamic deconstructive psychotherapy aims to activate and remediate neurocognitive self-capacities by facilitating elaboration of affect-laden interpersonal experiences and integration of attributions, as well as providing novel experiences in the patient-therapist relationship that promote self-other differentiation. Treatment involves weekly individual sessions for a predetermined period of time and follows sequential stages. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery across Biological Barriers

PubMed Central

Kievit, Forrest M.; Zhang, Miqin

2012-01-01

Cancer nanotheranostics aims to combine imaging and therapy of cancer through use of nanotechnology. The ability to engineer nanomaterials to interact with cancer cells at the molecular level can significantly improve the effectiveness and specificity of therapy to cancers that are currently difficult to treat. In particular, metastatic cancers, drug-resistant cancers, and cancer stem cells impose the greatest therapeutic challenge that requires targeted therapy to treat effectively. Targeted therapy can be achieved with appropriate designed drug delivery vehicles such as nanoparticles, adult stem cells, or T cells in immunotherapy. In this article, we first review the different types of materials commonly used to synthesize nanotheranostic particles and their use in imaging. We then discuss biological barriers that these nanoparticles encounter and must bypass to reach the target cancer cells, including the blood, liver, kidneys, spleen, and particularly the blood-brain barrier. We then review how nanotheranostics can be used to improve targeted delivery and treatment of cancer cells using nanoparticles, adult stem cells, and T cells in immunotherapy. Finally, we discuss development of nanoparticles to overcome current limitations in cancer therapy. PMID:21842473

Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies

PubMed Central

Brandi, Giovanni; Farioli, Andrea; Astolfi, Annalisa; Biasco, Guido; Tavolari, Simona

2015-01-01

Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease. PMID:26142706

Drug-targeting strategies in cancer therapy.

PubMed

Huang, P S; Oliff, A

2001-02-01

Genetic changes in cell-cycle, apoptotic, and survival pathways cause tumorigenesis, leading to significant phenotypic changes in transformed cells. These changes in the tumor environment - elevated expression of surface proteases, increased angiogenesis and glucuronidase activity - can be taken advantage of to improve the therapeutic index of existing cancer therapies. Targeting cytotoxics to tumor cells by enzymatic activation is a promising strategy for improving chemotherapeutics.

Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

PubMed Central

Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

2012-01-01

Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

[Targeted therapies in hepatocellular carcinomas: recent results and future development].

PubMed

Marijon, H; Faivre, S; Raymond, E

2009-05-01

Hepatocellular carcinoma (HCC) is one of the 5th most common cancers around the world with a limited number of systemic therapeutic options. Cytotoxic agents, hormonotherapy and immunotherapy have failed to demonstrate benefit compared to best supportive care in patients with advanced HCC. The recent development of targeted therapies provided hope for the treatment of advanced HCC. We reviewed phases II-III trials presented in 2007 and 2008. Results are promising with a clinical benefit reported with molecular therapies targeting EGF/EGFR and VEGF/VEGFR pathways.

Identification of the feedforward component in manual control with predictable target signals.

PubMed

Drop, Frank M; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus M; Mulder, Max

2013-12-01

In the manual control of a dynamic system, the human controller (HC) often follows a visible and predictable reference path. Compared with a purely feedback control strategy, performance can be improved by making use of this knowledge of the reference. The operator could effectively introduce feedforward control in conjunction with a feedback path to compensate for errors, as hypothesized in literature. However, feedforward behavior has never been identified from experimental data, nor have the hypothesized models been validated. This paper investigates human control behavior in pursuit tracking of a predictable reference signal while being perturbed by a quasi-random multisine disturbance signal. An experiment was done in which the relative strength of the target and disturbance signals were systematically varied. The anticipated changes in control behavior were studied by means of an ARX model analysis and by fitting three parametric HC models: two different feedback models and a combined feedforward and feedback model. The ARX analysis shows that the experiment participants employed control action on both the error and the target signal. The control action on the target was similar to the inverse of the system dynamics. Model fits show that this behavior can be modeled best by the combined feedforward and feedback model.

Identification of targets for rational pharmacological therapy in childhood craniopharyngioma.

PubMed

Gump, Jacob M; Donson, Andrew M; Birks, Diane K; Amani, Vladimir M; Rao, Karun K; Griesinger, Andrea M; Kleinschmidt-DeMasters, B K; Johnston, James M; Anderson, Richard C E; Rosenfeld, Amy; Handler, Michael; Gore, Lia; Foreman, Nicholas; Hankinson, Todd C

2015-05-21

Pediatric adamantinomatous craniopharyngioma (ACP) is a histologically benign but clinically aggressive brain tumor that arises from the sellar/suprasellar region. Despite a high survival rate with current surgical and radiation therapy (75-95 % at 10 years), ACP is associated with debilitating visual, endocrine, neurocognitive and psychological morbidity, resulting in excheptionally poor quality of life for survivors. Identification of an effective pharmacological therapy could drastically decrease morbidity and improve long term outcomes for children with ACP. Using mRNA microarray gene expression analysis of 15 ACP patient samples, we have found several pharmaceutical targets that are significantly and consistently overexpressed in our panel of ACP relative to other pediatric brain tumors, pituitary tumors, normal pituitary and normal brain tissue. Among the most highly expressed are several targets of the kinase inhibitor dasatinib - LCK, EPHA2 and SRC; EGFR pathway targets - AREG, EGFR and ERBB3; and other potentially actionable cancer targets - SHH, MMP9 and MMP12. We confirm by western blot that a subset of these targets is highly expressed in ACP primary tumor samples. We report here the first published transcriptome for ACP and the identification of targets for rational therapy. Experimental drugs targeting each of these gene products are currently being tested clinically and pre-clinically for the treatment of other tumor types. This study provides a rationale for further pre-clinical and clinical studies of novel pharmacological treatments for ACP. Development of mouse and cell culture models for ACP will further enable the translation of these targets from the lab to the clinic, potentially ushering in a new era in the treatment of ACP.

Evolving targeted therapies for right ventricular failure.

PubMed

Di Salvo, Thomas G

2015-01-01

Although right and left ventricular embryological origins, morphology and cardiodynamics differ, the notion of selectively targeted right ventricular therapies remains controversial. This review focuses on both the currently evolving pharmacologic agents targeting right ventricular failure (metabolic modulators, phosphodiesterase type V inhibitors) and future therapeutic approaches including epigenetic modulation by miRNAs, chromatin binding complexes, long non-coding RNAs, genomic editing, adoptive gene transfer and gene therapy, cell regeneration via cell transplantation and cell reprogramming and cardiac tissue engineering. Strategies for adult right ventricular regeneration will require a more holistic approach than strategies for adult left ventricular failure. Instances of right ventricular failure requiring global reconstitution of right ventricular myocardium, attractive approaches include: i) myocardial patches seeded with cardiac fibroblasts reprogrammed into cardiomyocytes in vivo by small molecules, miRNAs or other epigenetic modifiers; and ii) administration of miRNAs, lncRNAs or small molecules by non-viral vector delivery systems targeted to fibroblasts (e.g., episomes) to stimulate in vivo reprogramming of fibroblasts into cardiomyocytes. For selected heritable genetic myocardial diseases, genomic editing affords exciting opportunities for allele-specific silencing by site-specific directed silencing, mutagenesis or gene excision. Genomic editing by adoptive gene transfer affords similarly exciting opportunities for restoration of myocardial gene expression.

RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis

PubMed Central

Le Masson, Gwendal

2018-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS. PMID:29342921

RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis.

PubMed

Mathis, Stéphane; Le Masson, Gwendal

2018-01-15

Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS.

Molecular Approach to Targeted Therapy for Multiple Sclerosis.

PubMed

Sherbet, Gajanan V

2016-01-01

The development and evolution of targeted therapy to any disease require the identification of targets amenable to treatment of patients. Here the pathogenetic signalling systems involved in multiple sclerosis are scrutinised to locate nodes of deregulation and dysfunction in order to devise strategies of drug development for targeted intervention. Oliogoclonal bands (OCB) are isoelectric focusing profiles of immunoglobulins synthesised in the central nervous system. OCBs enable the diagnosis of multiple sclerosis with high sensitivity and specificity and are related to the course of the disease and progression. The OCB patterns can be linked with the expression of angiogenic molecular species. Angiogenic signalling which has also been implicated in demyelination provides the option of using angiogenesis inhibitors in disease control. The PI3K (phosphoinositide 3-kinase)/Akt axis has emerged with a key role in myelination with its demonstrable links with mTOR mediated transcription of downstream target genes. Inflammatory signals and innate and acquired immunity from the activation of NF-κB (nuclear factor κB) responsive genes are considered. NF-κB signalling could be implicated in myelination. The transcription factor STAT (signal transducers and activators of transcription) and the EBV (Epstein- Barr virus) transcription factor BZLF1 contributing significantly to the disease process are a major environmental factor linked to MS. EBV can activate TGF (transforming growth factor) and VEGF (vascular endothelial growth factor) signalling. EBV microRNAs are reviewed as signalling mediators of pathogenesis. Stem cell transplantation therapy has lately gained much credence, so the current status of mesenchymal and hematopoietic stem cell therapy is reviewed with emphasis on the differential expression immune-related genes and operation of signalling systems.

New perspectives on targeted therapy in ovarian cancer

PubMed Central

Coward, Jermaine IG; Middleton, Kathryn; Murphy, Felicity

2015-01-01

Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose) inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. PMID:25678824

Efficacy of Manual Therapy Including Neurodynamic Techniques for the Treatment of Carpal Tunnel Syndrome: A Randomized Controlled Trial.

PubMed

Wolny, Tomasz; Saulicz, Edward; Linek, Paweł; Shacklock, Michael; Myśliwiec, Andrzej

2017-05-01

The purpose of this randomized trial was to compare the efficacy of manual therapy, including the use of neurodynamic techniques, with electrophysical modalities on patients with mild and moderate carpal tunnel syndrome (CTS). The study included 140 CTS patients who were randomly assigned to the manual therapy (MT) group, which included the use of neurodynamic techniques, functional massage, and carpal bone mobilizations techniques, or to the electrophysical modalities (EM) group, which included laser and ultrasound therapy. Nerve conduction, pain severity, symptom severity, and functional status measured by the Boston Carpal Tunnel Questionnaire were assessed before and after treatment. Therapy was conducted twice weekly and both groups received 20 therapy sessions. A baseline assessment revealed group differences in sensory conduction of the median nerve (P < .01) but not in motor conduction (P = .82). Four weeks after the last treatment procedure, nerve conduction was examined again. In the MT group, median nerve sensory conduction velocity increased by 34% and motor conduction velocity by 6% (in both cases, P < .01). There was no change in median nerve sensory and motor conduction velocities in the EM. Distal motor latency was decreased (P < .01) in both groups. A baseline assessment revealed no group differences in pain severity, symptom severity, or functional status. Immediately after therapy, analysis of variance revealed group differences in pain severity (P < .01), with a reduction in pain in both groups (MT: 290%, P < .01; EM: 47%, P < .01). There were group differences in symptom severity (P < .01) and function (P < .01) on the Boston Carpal Tunnel Questionnaire. Both groups had an improvement in functional status (MT: 47%, P < .01; EM: 9%, P < .01) and a reduction in subjective CTS symptoms (MT: 67%, P < .01; EM: 15%, P < .01). Both therapies had a positive effect on nerve conduction, pain reduction, functional status, and subjective symptoms in

Accuracy of manual QRS duration assessment: its importance in patient selection for cardiac resynchronization and implantable cardioverter defibrillator therapy.

PubMed

Tomlinson, David R; Bashir, Yaver; Betts, Timothy R; Rajappan, Kim

2009-05-01

Patients with left ventricular systolic dysfunction and electrocardiographic QRS duration (QRSd) >or=120 ms may obtain symptomatic and prognostic benefits from cardiac resynchronization therapy (CRT). However, clinical trials do not describe the methods used to measure QRSd. We investigated the effect of electrocardiogram (ECG) display format and paper speed on the accuracy of manual QRSd assessment and concordance of manual QRSd with computer-calculated mean and maximal QRSd. Six cardiologists undertook QRSd measurements on ECGs, with computer-calculated mean QRSd close to 120 ms. Display formats were 12-lead, 6-limb, and 6-precordial leads, each at 25 and 50 mm/s. When the computer-calculated mean was used to define QRSd, manual assessment demonstrated 97 and 83% concordance at categorizing QRSd as < and >or=120 ms, respectively. Using the computer-calculated maximal QRSd, manual assessment demonstrated 83% concordance when QRSd was <120 ms and 19% concordance when QRSd was >or=120 ms. The six-precordial lead format demonstrated significantly less intra and inter-observer variabilities than the 12-lead, but this did not improve concordance rates. Manual QRSd assessments demonstrate significant variability, and concordance with computer-calculated measurement depends on whether QRSd is defined as the mean or maximal value. Consensus is required both on the most appropriate definition of QRSd and its measurement.

Theoretical and practical outline of the Copenhagen PACT narrative-based exercise counselling manual to promote physical activity in post-therapy cancer survivors.

PubMed

Midtgaard, Julie

2013-02-01

Sedentary behaviour and reduced exercise capacity are potential persisting effects of anti-cancer therapy that may predispose to serious health conditions. It is well-established that physical exercise may prevent some of these problems. However, the extent to which cancer survivors are able to adopt long-term physical activity habits depends largely on their motivation. This theoretical paper aims to outline how researchers and practitioners can draw from Antonovsky's salutogenetic theory and White & Epston's Narrative Therapy to develop and implement intervention efforts centered on promotion of long-term physical activity behaviour, while at the same time increasing the individual cancer survivor's sense of meaning and personal health resources. The Copenhagen PACT (Physical Activity after Cancer Treatment) Study targeting adoption and maintenance of regular physical activity in post-therapy cancer survivors is briefly presented including a brief review of the theoretical rationale behind the psychological component of the intervention, i.e. a narrative-based exercise counselling programme. Subsequently, particular attention is given to the core principles, different components and structure of the counselling manual including sample questions and examples of written documents that have emanated from the individual counselling sessions. The discussion includes consideration of some methodological challenges that arise when attempting to evaluate narrative-based interventions in the context of physical activity promotion in cancer rehabilitation and survivorship care.

Drug resistance to targeted therapies: déjà vu all over again.

PubMed

Groenendijk, Floris H; Bernards, René

2014-09-12

A major limitation of targeted anticancer therapies is intrinsic or acquired resistance. This review emphasizes similarities in the mechanisms of resistance to endocrine therapies in breast cancer and those seen with the new generation of targeted cancer therapeutics. Resistance to single-agent cancer therapeutics is frequently the result of reactivation of the signaling pathway, indicating that a major limitation of targeted agents lies in their inability to fully block the cancer-relevant signaling pathway. The development of mechanism-based combinations of targeted therapies together with non-invasive molecular disease monitoring is a logical way forward to delay and ultimately overcome drug resistance development. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The role and position of passive intervertebral motion assessment within clinical reasoning and decision-making in manual physical therapy: a qualitative interview study.

PubMed

van Trijffel, Emiel; Plochg, Thomas; van Hartingsveld, Frank; Lucas, Cees; Oostendorp, Rob A B

2010-06-01

Passive intervertebral motion (PIVM) assessment is a characterizing skill of manual physical therapists (MPTs) and is important for judgments about impairments in spinal joint function. It is unknown as to why and how MPTs use this mobility testing of spinal motion segments within their clinical reasoning and decision-making. This qualitative study aimed to explore and understand the role and position of PIVM assessment within the manual diagnostic process. Eight semistructured individual interviews with expert MPTs and three subsequent group interviews using manual physical therapy consultation platforms were conducted. Line-by-line coding was performed on the transcribed data, and final main themes were identified from subcategories. Three researchers were involved in the analysis process. Four themes emerged from the data: contextuality, consistency, impairment orientedness, and subjectivity. These themes were interrelated and linked to concepts of professionalism and clinical reasoning. MPTs used PIVM assessment within a multidimensional, biopsychosocial framework incorporating clinical data relating to mechanical dysfunction as well as to personal factors while applying various clinical reasoning strategies. Interpretation of PIVM assessment and subsequent decisions on manipulative treatment were strongly rooted within practitioners' practical knowledge. This study has identified the specific role and position of PIVM assessment as related to other clinical findings within clinical reasoning and decision-making in manual physical therapy in The Netherlands. We recommend future research in manual diagnostics to account for the multivariable character of physical examination of the spine.

The role and position of passive intervertebral motion assessment within clinical reasoning and decision-making in manual physical therapy: a qualitative interview study

PubMed Central

van Trijffel, Emiel; Plochg, Thomas; van Hartingsveld, Frank; Lucas, Cees; Oostendorp, Rob A B

2010-01-01

Passive intervertebral motion (PIVM) assessment is a characterizing skill of manual physical therapists (MPTs) and is important for judgments about impairments in spinal joint function. It is unknown as to why and how MPTs use this mobility testing of spinal motion segments within their clinical reasoning and decision-making. This qualitative study aimed to explore and understand the role and position of PIVM assessment within the manual diagnostic process. Eight semistructured individual interviews with expert MPTs and three subsequent group interviews using manual physical therapy consultation platforms were conducted. Line-by-line coding was performed on the transcribed data, and final main themes were identified from subcategories. Three researchers were involved in the analysis process. Four themes emerged from the data: contextuality, consistency, impairment orientedness, and subjectivity. These themes were interrelated and linked to concepts of professionalism and clinical reasoning. MPTs used PIVM assessment within a multidimensional, biopsychosocial framework incorporating clinical data relating to mechanical dysfunction as well as to personal factors while applying various clinical reasoning strategies. Interpretation of PIVM assessment and subsequent decisions on manipulative treatment were strongly rooted within practitioners’ practical knowledge. This study has identified the specific role and position of PIVM assessment as related to other clinical findings within clinical reasoning and decision-making in manual physical therapy in The Netherlands. We recommend future research in manual diagnostics to account for the multivariable character of physical examination of the spine. PMID:21655394

Factor XI as a target for antithrombotic therapy

PubMed Central

Bane, Charles E.; Gailani, David

2014-01-01

Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate Cancer...Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate

[Critical care nurse learning of continuous renal replacement therapy: the efficacy of a self-learning manual].

PubMed

Huang, Yi-Chen; Hsu, Li-Ling

2011-02-01

Many nurses have difficulty learning to use the complex, non-traditional, and regularly-updated critical care equipment. Failure to use such equipment properly can seriously compromise treatment and endanger patient health and lives. New self-learning materials for novice nurses are necessary to provide essential and effective guidance as a part of formal nursing training. Such materials can enhance the capabilities of critical care nurses and, thus, improve the general quality of critical care. The purpose of this research was to develop a continuous renal replacement therapy (CRRT)-themed self-learning manual that would provide easily absorbed and understood knowledge in an easy-to-carry format for ICU nursing staff. This study also investigated CCRT skill learning efficacy. This study adopted a quasi-experimental design with pretests and posttests. Purposive sampling generated a sample of 66 critical care nurses currently working at one hospital in Taipei City. Participants submitted a completed self-assessment survey that rated their command of continuous renal replacement therapy before and after the self-learning manual intervention. Survey data were analyzed using SPSS Version 17.0 for Windows. The two major findings derived from the study included: (1) The mean response score from the self-assessment survey filled out after the intervention was 91.06 and 79.75 (SD = 9.49 and 11.65), respectively, for experimental and control groups. Such demonstrated significant difference. (2) The mean posttest score after the intervention for the experimental group was 91.06 ± 9.49. This represents a significant increase of 10.35 ± 10.35 over their mean pretest score (80.71 ± 11.82). The experimental group showed other significant differences in terms of the CRRT self-assessment survey posttest. Self-learning manuals may be introduced in nursing education as useful aids and catalysts to achieve more effective and satisfying learning experiences.

Targeted alpha therapy using short-lived alpha-particles and the promise of nanobodies as targeting vehicle

PubMed Central

Dekempeneer, Yana; Keyaerts, Marleen; Krasniqi, Ahmet; Puttemans, Janik; Muyldermans, Serge; Lahoutte, Tony; D’huyvetter, Matthias; Devoogdt, Nick

2016-01-01

ABSTRACT Introduction: The combination of a targeted biomolecule that specifically defines the target and a radionuclide that delivers a cytotoxic payload offers a specific way to destroy cancer cells. Targeted radionuclide therapy (TRNT) aims to deliver cytotoxic radiation to cancer cells and causes minimal toxicity to surrounding healthy tissues. Recent advances using α-particle radiation emphasizes their potential to generate radiation in a highly localized and toxic manner because of their high level of ionization and short range in tissue. Areas covered: We review the importance of targeted alpha therapy (TAT) and focus on nanobodies as potential beneficial vehicles. In recent years, nanobodies have been evaluated intensively as unique antigen-specific vehicles for molecular imaging and TRNT. Expert opinion: We expect that the efficient targeting capacity and fast clearance of nanobodies offer a high potential for TAT. More particularly, we argue that the nanobodies’ pharmacokinetic properties match perfectly with the interesting decay properties of the short-lived α-particle emitting radionuclides Astatine-211 and Bismuth-213 and offer an interesting treatment option particularly for micrometastatic cancer and residual disease. PMID:27145158

Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy.

PubMed

Noujaim, Jonathan; Thway, Khin; Bajwa, Zia; Bajwa, Ayeza; Maki, Robert G; Jones, Robin L; Keller, Charles

2015-01-01

Epithelioid sarcoma (ES) is a soft tissue sarcoma of children and young adults for which the preferred treatment for localized disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.

Targeted therapies in hepatocellular carcinoma.

PubMed

Bronte, F; Bronte, G; Cusenza, S; Fiorentino, E; Rolfo, C; Cicero, G; Bronte, E; Di Marco, V; Firenze, A; Angarano, G; Fontana, T; Russo, A

2014-01-01

The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life.

Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

PubMed Central

Durcan, Laura; Petri, Michelle

2016-01-01

Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

Update on B-cell targeted therapies for systemic lupus erythematosus.

PubMed

Mok, Chi Chiu

2014-06-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by flares and remission, leading to accrual of organ damage over time as a result of persistent tissue inflammation and treatment-related complications. Novel therapies aiming at better treatment response and fewer adverse effects are being tested in the pipeline. This review summarizes the B-cell abnormalities observed in patients with SLE, and updates recent data on the efficacy and safety of B-cell targeted therapies in the treatment of SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed. The variability of clinical response to treatment in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan for patients with SLE should be individualized with the aim of eradicating disease activity, preventing flares and minimizing treatment-related complications. Despite the disappointment of recent clinical trials, B-cell remains the promising target of future SLE therapies. Results from ongoing clinical trials on B-cell targeted biological agents are eagerly awaited.

The effects of manual therapy or exercise therapy or both in people with hip osteoarthritis: a systematic review and meta-analysis.

PubMed

Sampath, Kesava Kovanur; Mani, Ramakrishnan; Miyamori, Takayuki; Tumilty, Steve

2016-12-01

To determine whether manual therapy or exercise therapy or both is beneficial for people with hip osteoarthritis in terms of reduced pain, improved physical function and improved quality of life. Databases such as Medline, AMED, EMBASE, CINAHL, SPORTSDiscus, PubMed, Cochrane Library, Web of Science, Physiotherapy Evidence Database, and SCOPUS were searched from their inception till September 2015. Two authors independently extracted and assessed the risk of bias in included studies. Standardised mean differences for outcome measures (pain, physical function and quality of life) were used to calculate effect sizes. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used for assessing the quality of the body of evidence for each outcome of interest. Seven trials (886 participants) that met the inclusion criteria were included in the meta-analysis. There was high quality evidence that exercise therapy was beneficial at post-treatment (pain-SMD-0.27,95%CI-0.5to-0.04;physical function-SMD-0.29,95%CI-0.47to-0.11) and follow-up (pain-SMD-0.24,95%CI- 0.41to-0.06; physical function-SMD-0.33,95%CI-0.5to-0.15). There was low quality evidence that manual therapy was beneficial at post-treatment (pain-SMD-0.71,95%CI-1.08to-0.33; physical function-SMD-0.71,95%CI-1.08to-0.33) and follow-up (pain-SMD-0.43,95%CI-0.8to-0.06; physical function-SMD-0.47,95%CI-0.84to-0.1). Low quality evidence indicated that combined treatment was beneficial at post-treatment (pain-SMD-0.43,95%CI-0.78to-0.08; physical function-SMD-0.38,95%CI-0.73to-0.04) but not at follow-up (pain-SMD0.25,95%CI-0.35to0.84; physical function-SMD0.09,95%CI-0.5to0.68). There was no effect of any interventions on quality of life. An Exercise therapy intervention provides short-term as well as long-term benefits in terms of reduction in pain, and improvement in physical function among people with hip osteoarthritis. The observed magnitude of the treatment effect would be considered

Oncogenic drivers, targeted therapies, and acquired resistance in non-small-cell lung cancer.

PubMed

Gower, Arjan; Wang, Yisong; Giaccone, Giuseppe

2014-07-01

In the past decade, a shift toward targeted therapies in non-small-cell lung cancer following molecular profiling has dramatically changed the way advanced adenocarcinoma is treated. However, tumor cells inevitably acquire resistance to such therapies, circumventing any sustained clinical benefit. As the genomic classification of lung cancer continues to evolve and as the mechanisms of acquired resistance to targeted therapies become elucidated and more improved target-specific drugs come into sight, the future will see more promising results from the clinic through the development of new therapeutic strategies to overcome, or prevent the development of, resistance for lung cancer patients.

[Molecular-targeted therapy for neurodegenerative diseases].

PubMed

Sobue, Gen

2009-11-01

Neurodegenerative diseases have been construed as incurable disorders. However, therapeutic development for these diseases is now facing a turning point: analyses of cellular and animal models have provided insights into pathogenesis of neurodegenerative diseases, and have indicated rational therapeutic approaches to them. Therefore, how to realize molecular targeted therapy for neurodegenerative diseases is becoming one of the most challenging issues in the clinical neurology. Primarily, pathophysiological understanding of the disease from basic science is the first step. For the successful clinical trials, effective trial design, sufficient economic and social support, and education are indispensable. The development of androgen deprivation therapy for spinal and bulbar muscular atrophy (SBMA) is a representative study in this field. SBMA is a hereditary neurodegenerative disease caused by expansion of a trinucleotide CAG repeat in the first exon of the androgen receptor (AR) gene. There is increasing evidence that testosterone, the ligand of AR, plays a pivotal role in the neurodegeneration in SBMA. The striking success of androgen deprivation therapy in SBMA mouse models has been translated into phase 2, and then phase 3, clinical trials.

Cancer gene therapy with targeted adenoviruses.

PubMed

Bachtarzi, Houria; Stevenson, Mark; Fisher, Kerry

2008-11-01

Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. This manuscript aims to provide an overview of the techniques currently under development for improving adenovirus delivery to malignant cells in vivo. Primary research articles reporting improvements in adenoviral gene delivery are described. Strategies include genetic modification of viral coat proteins, non-genetic modifications including polymer encapsulation approaches and pharmacological interventions. Reprogramming adenovirus tropism in vitro has been convincingly demonstrated using a range of genetic and physical strategies. These studies have provided new insights into our understanding of virology and the field is progressing. However, there are still some limitations that need special consideration before adenovirus-targeted cancer gene therapy emerges as a routine treatment in the clinical setting.

An overview of targeted alpha therapy with 225Actinium and 213Bismuth.

PubMed

Morgenstern, Alfred; Apostolidis, Christos; Kratochwil, Clemens; Sathekge, Mike; Krolicki, Leszek; Bruchertseifer, Frank

2018-05-01

Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA-617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy. This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Experiences of Older Adults With Mobile Phone Text Messaging as Reminders of Home Exercises After Specialized Manual Therapy for Recurrent Low Back Pain: A Qualitative Study.

PubMed

Lilje, Stina Charlotta; Olander, Ewy; Berglund, Johan; Skillgate, Eva; Anderberg, Peter

2017-03-30

Clinical experience of manual therapy for musculoskeletal pain is that patients often suffer from recurrent pain and disorders, but that they do not continue to perform their physical home exercises when they are free from symptoms. The chance of positive long-term effects of manual therapy would probably increase if patients were reminded that they are to continue to perform their exercises. Mobile phone text messaging (short messaging service, SMS) is increasingly used as an innovative intervention to remind patient to exercise. However, there are only a few studies on such interventions in the field of low back pain (LBP). Qualitative studies of patients' experiences of receiving text messages as reminders of home exercises after manual treatment for recurrent LBP have to the best of our knowledge never been published. The aim of this study was to explore older persons' common experiences of receiving reminders of home exercises through mobile phone text messaging after specialized manual therapy for recurrent LBP. A total of 7 men and 8 women (67-86 years), who had sought specialized manual therapy (Naprapathic manual therapy) for recurrent LBP were included in the study. Individual one-way text messages as reminders of home exercises (to be performed on a daily basis) were sent to each patient every third day for 3 weeks, then once a week for another 2 weeks. Semistructured interviews with 2 broad, open-ended questions were held and data were analyzed with systematic text condensation, based on Giorgi's principles of psychological phenomenological analysis. The participants appreciated the messages, which were perceived as timely and usable, and also stimulated memorizing. The messages made the participants reflect on the aim of the exercise, value of being reminded, and on their improvement in pain. During the interviews, the participants created their own routines for continued adherence to the exercises. It seems plausible that mobile phone text messaging

The offer of chemistry to targeted therapy in cancer.

PubMed

Jemel, Ikram; Jellali, Karim; Elloumi, Jihene; Aifa, Sami

2011-12-01

Cancer therapy is facing the big challenge of destroying selectively tumour cells without harming the normal tissues. Chemotherapy was trying from the beginning to kill malignant cells because of their proliferative activity since normal cells are in general quiescent. Meanwhile side effects were produced due to the destruction of some normal cells that need regular proliferation. The discovery of biomarkers led to the identification of molecular targets within tumour cells in order to kill them selectively. Chemistry followed the progress of biomarkers biotechnology by the production of target specific antagonists which were the subject of many patents. Meanwhile novel problems of tumour resistance appeared and made the battle against cancer a non stop development of new strategies and new weapons. As a consequence, paralleled activities of patenting biomarkers and chemical antagonists are continuously generated. The offer of chemistry does not actually limit the efficiency of Targeted therapy but the identification of biomarkers is still missing the exclusive specificity to tumour cells.

Effectiveness of manual therapies: the UK evidence report

PubMed Central

2010-01-01

Background The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions. Methods The conclusions are based on the results of systematic reviews of randomized clinical trials (RCTs), widely accepted and primarily UK and United States evidence-based clinical guidelines, plus the results of all RCTs not yet included in the first three categories. The strength/quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs. Results By September 2009, 26 categories of conditions were located containing RCT evidence for the use of manual therapy: 13 musculoskeletal conditions, four types of chronic headache and nine non-musculoskeletal conditions. We identified 49 recent relevant systematic reviews and 16 evidence-based clinical guidelines plus an additional 46 RCTs not yet included in systematic reviews and guidelines. Additionally, brief references are made to other effective non-pharmacological, non-invasive physical treatments. Conclusions Spinal manipulation/mobilization is effective in adults for: acute, subacute, and chronic low back pain; migraine and cervicogenic headache; cervicogenic dizziness; manipulation/mobilization is effective for several extremity joint conditions; and thoracic manipulation/mobilization is effective for acute/subacute neck pain. The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration, and for manipulation/mobilization for mid back pain, sciatica, tension-type headache, coccydynia, temporomandibular joint disorders, fibromyalgia, premenstrual syndrome, and pneumonia in older adults. Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham

EGFR Targeted Therapies and Radiation: Optimizing Efficacy by Appropriate Drug Scheduling and Patient Selection

PubMed Central

Cuneo, Kyle C.; Nyati, Mukesh K.; Ray, Dipankar; Lawrence, Theodore S.

2015-01-01

The epidermal growth factor receptor (EGFR) plays an important role in tumor progression and treatment resistance for many types of malignancies including head and neck, colorectal, and nonsmall cell lung cancer. Several EGFR targeted therapies are efficacious as single agents or in combination with chemotherapy. Given the toxicity associated with chemoradiation and poor outcomes seen in several types of cancers, combinations of EGFR targeted agents with or without chemotherapy have been tested in patients receiving radiation. To date, the only FDA approved use of an anti-EGFR therapy in combination with radiation therapy is for locally advanced head and neck cancer. Given the important role EGFR plays in lung and colorectal cancer and the benefit of EGFR inhibition combined with chemotherapy in these disease sites, it is perplexing why EGFR targeted therapies in combination with radiation or chemoradiation have not been more successful. In this review we summarize the clinical findings of EGFR targeted therapies combined with radiation and chemoradiation regimens. We then discuss the interaction between EGFR and radiation including radiation induced EGFR signaling, the effect of EGFR on DNA damage repair, and potential mechanisms of radiosensitization. Finally, we examine the potential pitfalls with scheduling EGFR targeted therapies with chemoradiation and the use of predictive biomarkers to improve patient selection. PMID:26205191

Applying Computer Models to Realize Closed-Loop Neonatal Oxygen Therapy.

PubMed

Morozoff, Edmund; Smyth, John A; Saif, Mehrdad

2017-01-01

Within the context of automating neonatal oxygen therapy, this article describes the transformation of an idea verified by a computer model into a device actuated by a computer model. Computer modeling of an entire neonatal oxygen therapy system can facilitate the development of closed-loop control algorithms by providing a verification platform and speeding up algorithm development. In this article, we present a method of mathematically modeling the system's components: the oxygen transport within the patient, the oxygen blender, the controller, and the pulse oximeter. Furthermore, within the constraints of engineering a product, an idealized model of the neonatal oxygen transport component may be integrated effectively into the control algorithm of a device, referred to as the adaptive model. Manual and closed-loop oxygen therapy performance were defined in this article by 3 criteria in the following order of importance: percent duration of SpO2 spent in normoxemia (target SpO2 ± 2.5%), hypoxemia (less than normoxemia), and hyperoxemia (more than normoxemia); number of 60-second periods <85% SpO2 and >95% SpO2; and number of manual adjustments. Results from a clinical evaluation that compared the performance of 3 closed-loop control algorithms (state machine, proportional-integral-differential, and adaptive model) with manual oxygen therapy on 7 low-birth-weight ventilated preterm babies, are presented. Compared with manual therapy, all closed-loop control algorithms significantly increased the patients' duration in normoxemia and reduced hyperoxemia (P < 0.05). The number of manual adjustments was also significantly reduced by all of the closed-loop control algorithms (P < 0.05). Although the performance of the 3 control algorithms was equivalent, it is suggested that the adaptive model, with its ease of use, may have the best utility.

Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy

NASA Astrophysics Data System (ADS)

Zhu, Dao-Ming; Xie, Wei; Xiao, Yu-Sha; Suo, Meng; Zan, Ming-Hui; Liao, Qing-Quan; Hu, Xue-Jia; Chen, Li-Ben; Chen, Bei; Wu, Wen-Tao; Ji, Li-Wei; Huang, Hui-Ming; Guo, Shi-Shang; Zhao, Xing-Zhong; Liu, Quan-Yan; Liu, Wei

2018-02-01

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam-RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.

Manual therapy in joint and nerve structures combined with exercises in the treatment of recurrent ankle sprains: A randomized, controlled trial.

PubMed

Plaza-Manzano, Gustavo; Vergara-Vila, Marta; Val-Otero, Sandra; Rivera-Prieto, Cristina; Pecos-Martin, Daniel; Gallego-Izquierdo, Tomás; Ferragut-Garcías, Alejandro; Romero-Franco, Natalia

2016-12-01

Recurrent ankle sprains often involve residual symptoms for which subjects often perform proprioceptive or/and strengthening exercises. However, the effectiveness of mobilization to influence important nerve structures due to its anatomical distribution like tibial and peroneal nerves is unclear. To analyze the effects of proprioceptive/strengthening exercises versus the same exercises and manual therapy including mobilizations to influence joint and nerve structures in the management of recurrent ankle sprains. A randomized single-blind controlled clinical trial. Fifty-six patients with recurrent ankle sprains and regular sports practice were randomly assigned to experimental or control group. The control group performed 4 weeks of proprioceptive/strengthening exercises; the experimental group performed 4 weeks of the same exercises combined with manual therapy (mobilizations to influence joint and nerve structures). Pain, self-reported functional ankle instability, pressure pain threshold (PPT), ankle muscle strength, and active range of motion (ROM) were evaluated in the ankle joint before, just after and one month after the interventions. The within-group differences revealed improvements in all of the variables in both groups throughout the time. Between-group differences revealed that the experimental group exhibited lower pain levels and self-reported functional ankle instability and higher PPT, ankle muscle strength and ROM values compared to the control group immediately after the interventions and one month later. A protocol involving proprioceptive and strengthening exercises and manual therapy (mobilizations to influence joint and nerve structures) resulted in greater improvements in pain, self-reported functional joint stability, strength and ROM compared to exercises alone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeted anti-IL-13 therapies in asthma: current data and future perspectives.

PubMed

Ntontsi, Polyxeni; Papathanassiou, Evgenia; Loukides, Stelios; Bakakos, Petros; Hillas, Georgios

2018-02-01

The identification of patients with severe asthma who will benefit from a personalized management approach remains an unmet need. Interleukin-13 (IL-13) is a cytokine possessing a significant role in asthma pathogenesis and progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13 and IL-4 receptors are mainly proposed as add-on therapy in patients with T H 2-high inflammation with uncontrolled asthma despite maximum therapy. Areas covered: The role of IL-13 in airway inflammation in severe asthma, the targeted anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment are discussed. Expert opinion: New effective individualized therapies in severe asthma are urgently needed to block specific inflammatory pathways using monoclonal antibodies. Studies on anti-IL-13 therapies showed that asthmatic patients could benefit from this novel targeted therapy as far as lung function and exacerbation rate are concerned. T H 2-high and especially periostin-high groups of asthmatics with moderate-to-severe uncontrolled asthma seem to compose the group that could benefit from anti-IL-13 therapy. Targeting IL-13 alone may not be sufficient to achieve asthma control. Inhibition of IL-13 and IL-4 with mabs may be more encouraging and patients will probably have additional benefits from these therapeutic interventions because of IL-13/IL-4 overlapping actions in asthma pathophysiology.

Targeting the undruggable: Advances and obstacles in current RNAi therapy

PubMed Central

Wu, Sherry Y.; Lopez-Berestein, Gabriel; Calin, George A.; Sood, Anil K.

2014-01-01

RNA interference (RNAi) therapeutics represents a rapidly emerging platform for personalized cancer treatment. Recent advances in delivery, target selection, and safety of RNAi cancer therapy provide unprecedented opportunities for clinical translation. Here, we discuss these advances and present strategies for making RNAi-based therapy a viable part of cancer management. PMID:24920658

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

PubMed Central

Wachsmann, Jason; Peng, Fangyu

2016-01-01

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

The Insulin Receptor: A New Target for Cancer Therapy

PubMed Central

Malaguarnera, Roberta; Belfiore, Antonino

2011-01-01

A large body of evidences have shown that both the IGF-I receptor (IGF-IR) and the insulin receptor (IR) play a role in cancer development and progression. In particular, IR overactivation by IGF-II is common in cancer cells, especially in dedifferentiated/stem-like cells. In spite of these findings, until very recently, only IGF-IR but not IR has been considered a target in cancer therapy. Although several preclinical studies have showed a good anti-cancer activity of selective anti-IGF-IR drugs, the results of the clinical first trials have been disappointing. In fact, only a small subset of malignant tumors has shown an objective response to these therapies. Development of resistance to anti-IGF-IR drugs may include upregulation of IR isoform A (IR-A) in cancer cells and its overactivation by increased secretion of autocrine IGF-II. These findings have led to the concept that co-targeting IR together with IGF-IR may increase therapy efficacy and prevent adaptive resistance to selective anti-IGF-IR drugs. IR blockade should be especially considered in tumors with high IR-A:IGF-IR ratio and high levels of autocrine IGF-II. Conversely, insulin sensitizers, which ameliorate insulin resistance associated with metabolic disorders and cancer treatments, may have important implications for cancer prevention and management. Only few drugs co-targeting the IR and IGF-IR are currently available. Ideally, future IR targeting strategies should be able to selectively inhibit the tumor promoting effects of IR without impairing its metabolic effects. PMID:22654833

Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

PubMed Central

Patel, Jesal C.; Maughan, Benjamin L.; Agarwal, Archana M.; Batten, Julia A.; Zhang, Tian Y.; Agarwal, Neeraj

2013-01-01

Androgen deprivation therapy (ADT) with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC) and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR) signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700), and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials. PMID:23819055

Stroma Breaking Theranostic Nanoparticles for Targeted Pancreatic Cancer Therapy

Cancer.gov

This project develops a dual-targeted and stroma breaking theranostic nanoparticle platform to address an unmet, clinical challenge of poor drug delivery efficiency in the application of nanomedicine to cancer therapy.

Immune Effects of Chemotherapy, Radiation, and Targeted Therapy and Opportunities for Combination With Immunotherapy.

PubMed

Wargo, Jennifer A; Reuben, Alexandre; Cooper, Zachary A; Oh, Kevin S; Sullivan, Ryan J

2015-08-01

There have been significant advances in cancer treatment over the past several years through the use of chemotherapy, radiation therapy, molecularly targeted therapy, and immunotherapy. Despite these advances, treatments such as monotherapy or monomodality have significant limitations. There is increasing interest in using these strategies in combination; however, it is not completely clear how best to incorporate molecularly targeted and immune-targeted therapies into combination regimens. This is particularly pertinent when considering combinations with immunotherapy, as other types of therapy may have significant impact on host immunity, the tumor microenvironment, or both. Thus, the influence of chemotherapy, radiation therapy, and molecularly targeted therapy on the host anti-tumor immune response and the host anti-host response (ie, autoimmune toxicity) must be taken into consideration when designing immunotherapy-based combination regimens. We present data related to many of these combination approaches in the context of investigations in patients with melanoma and discuss their potential relationship to management of patients with other tumor types. Importantly, we also highlight challenges of these approaches and emphasize the need for continued translational research. Copyright © 2015 Elsevier Inc. All rights reserved.

Randomized controlled trial comparing cerebral perfusion pressure-targeted therapy versus intracranial pressure-targeted therapy for raised intracranial pressure due to acute CNS infections in children.

PubMed

Kumar, Ramesh; Singhi, Sunit; Singhi, Pratibha; Jayashree, Muralidharan; Bansal, Arun; Bhatti, Anuj

2014-08-01

In children with acute CNS infection, management of raised intracranial pressure improves mortality and neuromorbidity. We compared cerebral perfusion pressure-targeted approach with the conventional intracranial pressure-targeted approach to treat raised intracranial pressure in these children. Prospective open-label randomized controlled trial. PICU in a tertiary care academic institute. Hundred ten children (1-12 yr) with acute CNS infections having raised intracranial pressure and a modified Glasgow Coma Scale score less than or equal to 8 were enrolled. Patients were randomized to receive either cerebral perfusion pressure-targeted therapy (n = 55) (maintaining cerebral perfusion pressure ≥ 60 mm Hg, using normal saline bolus and vasoactive therapy-dopamine, and if needed noradrenaline) or intracranial pressure-targeted therapy (n = 55) (maintaining intracranial pressure < 20 mm Hg using osmotherapy while ensuring normal blood pressure). The primary outcome was mortality up to 90 days after discharge from PICU. Secondary outcome was modified Glasgow Coma Scale score at 72 hours after enrollment, length of PICU stay, duration of mechanical ventilation, and hearing deficit and functional neurodisability at discharge and 90-day follow-up. A 90-day mortality in intracranial pressure group (38.2%) was significantly higher than cerebral perfusion pressure group (18.2%; relative risk = 2.1; 95% CI, 1.09-4.04; p = 0.020). The cerebral perfusion pressure group in comparison with intracranial pressure group had significantly higher median (interquartile range) modified Glasgow Coma Scale score at 72 hours (10 [8-11] vs 7 [4-9], p < 0.001), shorter length of PICU stay (13 d [10.8-15.2 d] vs. 18 d [14.5-21.5 d], p = 0.002) and mechanical ventilation (7.5 d [5.4-9.6 d] vs. 11.5 d [9.5-13.5 d], p = 0.003), lower prevalence of hearing deficit (8.9% vs 37.1%; relative risk = 0.69; 95% CI, 0.53-0.90; p = 0.005), and neurodisability at discharge from PICU (53.3% vs. 82

Targeting Trypsin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model

DTIC Science & Technology

2016-10-01

Award Number: W81XWH-15-1-0257 TITLE: Targeting Trypsin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model PRINCIPAL...AND SUBTITLE Targeting Trypsin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model 5a. CONTRACT NUMBER 5b. GRANT NUMBER...remains the same since it is covered under the institutional review. We set up monthly video conferences with our partnership PI to discuss any

Labelling of 90Y- and 177Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated, and Fully Automated Synthesis.

PubMed

Iori, Michele; Capponi, Pier C; Rubagotti, Sara; Esposizione, Luca Rosario; Seemann, Johanna; Pitzschler, Riccardo; Dreger, Thorsten; Formisano, Debora; Grassi, Elisa; Fioroni, Federica; Versari, Annibale; Asti, Mattia

2017-01-01

In spite of the hazard due to the radiation exposure, preparation of 90 Y- and 177 Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177 Lu- and 90 Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617) was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90 Y- and 177 Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90 Y-DOTATOC were 96.2 ± 4.9%, 90.3 ± 5.6%, and 82.0 ± 8.4%, while for 177 Lu-DOTATOC they were 98.3%  ± 0.6, 90.8%  ± 8.3, and 83.1 ± 5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15 ± 0.4 mSv/GBq, 0.04 ± 0.1 mSv/GBq, and 0.11 ± 0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02 ± 0.008 mSv/GBq, 0.01 ± 0.03 mSv/GBq, and 0.01 ± 0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system.

TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy

PubMed Central

Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F.; Tang, Jen-Yang

2017-01-01

Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer. PMID:28708091

TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy.

PubMed

Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F; Tang, Jen-Yang; Chang, Hsueh-Wei

2017-07-14

Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer.

Targeted Immune Therapy of Ovarian Cancer

PubMed Central

Knutson, Keith L.; Karyampudi, Lavakumar; Lamichhane, Purushottam; Preston, Claudia

2014-01-01

Clinical outcomes, such as recurrence free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies. PMID:25544369

Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial.

PubMed

Khan, Fakhar Z; Virdee, Mumohan S; Palmer, Christopher R; Pugh, Peter J; O'Halloran, Denis; Elsik, Maros; Read, Philip A; Begley, David; Fynn, Simon P; Dutka, David P

2012-04-24

This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead

Aptamers: Active Targeting Ligands for Cancer Diagnosis and Therapy

PubMed Central

Wu, Xu; Chen, Jiao; Wu, Min; Zhao, Julia Xiaojun

2015-01-01

Aptamers, including DNA, RNA and peptide aptamers, are a group of promising recognition units that can specifically bind to target molecules and cells. Due to their excellent specificity and high affinity to targets, aptamers have attracted great attention in various fields in which selective recognition units are required. They have been used in biosensing, drug delivery, disease diagnosis and therapy (especially for cancer treatment). In this review, we summarized recent applications of DNA and RNA aptamers in cancer theranostics. The specific binding ability of aptamers to cancer-related markers and cancer cells ensured their high performance for early diagnosis of cancer. Meanwhile, the efficient targeting ability of aptamers to cancer cells and tissues provided a promising way to deliver imaging agents and drugs for cancer imaging and therapy. Furthermore, with the development of nanoscience and nanotechnology, the conjugation of aptamers with functional nanomaterials paved an exciting way for the fabrication of theranostic agents for different types of cancers, which might be a powerful tool for cancer treatment. PMID:25699094

Iodine-131-labeled, transferrin-capped polypyrrole nanoparticles for tumor-targeted synergistic photothermal-radioisotope therapy.

PubMed

Song, Xuejiao; Liang, Chao; Feng, Liangzhu; Yang, Kai; Liu, Zhuang

2017-08-22

Combining different therapeutic functions within single tumor-targeted nanoscale delivery systems is promising to overcome the limitations of conventional cancer therapies. Herein, transferrin that recognizes transferrin receptors up-regulated on tumor cells is pre-labeled with iodine-131 ( 131 I) and then utilized as the stabilizer in the fabrication of polypyrrole (PPy) nanoparticles. The obtained transferrin-capped PPy@Tf- 131 I nanoparticles could be used for tumor-targeted radioisotope therapy (RIT) and photothermal therapy (PTT), by employing beta-emission from 131 I and the intrinsic high near-infrared (NIR) absorbance of PPy, respectively. Owing to the transferrin-mediated tumor targeting, PPy@Tf- 131 I nanoparticles exhibit obviously enhanced in vitro cancer cell binding and in vivo tumor uptake compared to its non-targeting counterpart. The combined RIT and PTT based on PPy@Tf- 131 I nanoparticles is then conducted, achieving a remarkable synergistic therapeutic effect. This work thus demonstrates a rather simple one-step approach to fabricate tumor-targeting nanoparticles based on protein-capped conjugated polymers, promising for combination cancer therapy with great efficacy and high safety.

Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

NASA Astrophysics Data System (ADS)

Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

2011-06-01

The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

Targeted Therapies for Autosomal Dominant Polycystic Kidney Disease.

PubMed

Stayner, Cherie; Brooke, Darby G; Bates, Michael; Eccles, Michael R

2018-05-07

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease in humans, affecting approximately 1 in 500 people. ADPKD is characterized by cyst growth in the kidney leading to progressive parenchymal damage and is the underlying pathology in approximately 10% of patients requiring hemodialysis or transplantation for end-stage kidney disease. The two proteins that are mutated in ADPKD, polycystin-1 and polycystin-2, form a complex located on the primary cilium and the plasma membrane to facilitate calcium ion release in the cell. There is currently no Food and Drug Administration (FDA)-approved therapy to cure or slow the progression of the disease. Rodent ADPKD models do not completely mimic the human disease, and therefore preclinical results have not always successfully translated to the clinic. Moreover, the toxicity of many of these potential therapies has led to patient withdrawals from clinical trials. Here, we review compounds in a clinical trial for treating ADPKD, and we examine the feasibility of using a kidney-targeted approach, with potential for broadening the therapeutic window, decreasing treatment-associated toxicity and increasing the efficacy of agents that have demonstrated activity in animal models. We make recommendations for integrating kidney-targeted therapies with current treatment regimes, to achieve a combined approach to treating ADPKD. Many compounds are currently in clinical trial for ADPKD, yet to date, none are FDA-approved for treating this disease. Patients could benefit from efficacious pharmacotherapy, especially if it can be kidney-targeted, and intensive efforts continue to be focused on this goal. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

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

Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

2012-01-15

Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTV{sub P}) and involved lymph nodes (GTV{sub LN}) to simulate the localization process in image-guidedmore » radiation therapy. Techniques included ''standard'' (direct registration of weekly images to a planning CT), ''seeded'' (manual prealignment of targets to guide standard registration), ''transitive-based'' (alignment of pretreatment and planning CTs through one or more intermediate images), and ''rereferenced'' (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 {+-} 5.4 mm and 5.4 {+-} 3.4 mm for the GTV{sub P} and GTV{sub LN}, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTV{sub P} centroid LE to 4.7 {+-} 3.7 mm (p = 0.011) and 4.3 {+-} 2.5 mm (p < 1 x 10{sup -3}), respectively, but the smallest GTV{sub P} LE of 2.4 {+-} 2.1 mm was provided by rereferenced registration (p < 1 x 10{sup -6}). Standard registration significantly reduced GTV{sub LN} centroid LE to 3.2 {+-} 2.5 mm (p < 1 x 10{sup -3}) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE

New targets and therapies for gastrointestinal stromal tumors.

PubMed

Wozniak, Agnieszka; Gebreyohannes, Yemarshet K; Debiec-Rychter, Maria; Schöffski, Patrick

2017-12-01

The majority of gastrointestinal stromal tumors (GIST) are driven by an abnormal receptor tyrosine kinase (RTK) signaling, occurring mainly due to somatic mutations in KIT or platelet derived growth factor receptor alpha (PDGFRA). Although the introduction of tyrosine kinase inhibitors (TKIs) has revolutionized therapy for GIST patients, with time the vast majority of them develop TKI resistance. Advances in understanding the molecular background of GIST resistance allows for the identification of new targets and the development of novel strategies to overcome or delay its occurrence. Areas covered: The focus of this review is on novel, promising therapeutic approaches to overcome heterogeneous resistance to registered TKIs. These approaches involve new TKIs, including drugs specific for a mutated form of KIT/PDGFRA, drugs with inhibitory effect against multiple RTKs, compounds targeting dysregulated downstream signaling pathways, drugs affecting KIT expression and degradation, inhibitors of cell cycle, and immunotherapeutics. Expert commentary: As the resistance to standard TKI treatment can be heterogeneous, a combinational approach for refractory GIST could be beneficial. Moreover, the understanding of the molecular background of resistant disease would allow development of a more personalized approach for these patients and their response to targeted therapy could be monitored closely using 'liquid biopsy'.

Castration-resistant prostate cancer: targeted therapies.

PubMed

Leo, S; Accettura, C; Lorusso, V

2011-01-01

Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Novel targeted therapies in clinical trials were identified from registries. The Medline database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression have translated into a variety of treatment approaches. Agents targeting androgen receptor activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase III trials for patients with CRPC. There has been an increase in the understanding of the mechanisms of progression of CRPC. A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. Copyright © 2011 S. Karger AG, Basel.

New targeted therapies for indolent B-cell malignancies in older patients.

PubMed

Krem, Maxwell M; Gopal, Ajay K

2015-01-01

Molecularly targeted agents have become an established component of the treatment of indolent B-cell malignancies (iNHL). iNHL disproportionately affects older adults, so treatments that have excellent tolerability and efficacy across multiple lines of therapy are in demand. The numbers and classes of targeted therapies for iNHL have proliferated rapidly in recent years; classes of agents that show promise for older patients with iNHL include anti-CD20 antibodies, phosphatidyl-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway inhibitors, immunomodulators, proteasome inhibitors, epigenetic modulators, and immunotherapies. Here, we review the proposed mechanisms of action, efficacy, and tolerability of novel agents for iNHL, with an emphasis on their applicability to older patients.

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

PubMed Central

Nagórniewicz, Beata; Prakash, Jai

2016-01-01

Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis. PMID:27999454

Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov

PubMed Central

Xu, Jun; Lee, Hee-Jin; Zeng, Jia; Wu, Yonghui; Zhang, Yaoyun; Huang, Liang-Chin; Johnson, Amber; Holla, Vijaykumar; Bailey, Ann M; Cohen, Trevor; Meric-Bernstam, Funda; Bernstam, Elmer V

2016-01-01

Objective: Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. Methods: We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. Results and Discussion: The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy. PMID:27013523

Nanozeolite bioconjugates labeled with 223Ra for targeted alpha therapy.

PubMed

Piotrowska, Agata; Męczyńska-Wielgosz, Sylwia; Majkowska-Pilip, Agnieszka; Koźmiński, Przemysław; Wójciuk, Grzegorz; Cędrowska, Edyta; Bruchertseifer, Frank; Morgenstern, Alfred; Kruszewski, Marcin; Bilewicz, Aleksander

2017-04-01

Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Among the many α emitters, 223 Ra exhibits very attractive nuclear properties for application in radionuclide therapy. The decay of this radioisotope and its daughters is accompanied by the emission of four α-particles, releasing 27.9MeV of cumulative energy. Unfortunately the lack of an appropriate bifunctional ligand for radium has so far been a main obstacle for the application of 223 Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite-Substance P bioconjugates as vehicles for 223 Ra radionuclides for targeted α therapy. The sodium form of an A-type of nanozeolite (NaA) was synthesized using the template method. Next, the nanozeolite particles were conjugated to the Substance P (5-11) peptide fragment, which targets NK-1 receptors on glioma cells. The obtained bioconjugate was characterized by transmission emission spectroscopy, thermogravimetric analysis and dynamic light scattering analysis. The NaA-silane-PEG-SP(5-11) bioconjugates were labeled with 223 Ra by exchange of the Na + cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested. The 223 Ra-labeled nanozeolite bioconjugate almost quantitatively retains 223 Ra in vitro after 6days, while the retention of decay products varies from 90 to 95%. The synthesized 223 RaA-silane-PEG-SP(5-11) showed high receptor affinity toward NK-1 receptor expressing glioma cells and exhibited a high cytotoxic effect in vitro. Substance P functionalized nanozeolite-A represents a viable solution for the use of the 223 Ra in vivo generator as a therapeutic construct for targeting glioma cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Engineering liposomal nanoparticles for targeted gene therapy.

PubMed

Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

2017-08-01

Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

PubMed Central

Mavroudi, Maria; Zarogoulidis, Paul; Porpodis, Konstantinos; Kioumis, Ioannis; Lampaki, Sofia; Yarmus, Lonny; Malecki, Raf; Zarogoulidis, Konstantinos; Malecki, Marek

2014-01-01

Introduction Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The statistics speak for themselves with the grim reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem cells’ guided gene therapy. Review of therapeutic strategies in preclinical and clinical trials Stem cells have the unique potential for self renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells only. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for

Genetic tumor profiling and genetically targeted cancer therapy.

PubMed

Goetsch, Cathleen M

2011-02-01

To discuss how understanding and manipulation of tumor genetics information and technology shapes cancer care today and what changes might be expected in the near future. Published articles, web resources, clinical practice. Advances in our understanding of genes and their regulation provide a promise of more personalized cancer care, allowing selection of the most safe and effective therapy in an individual situation. Rapid progress in the technology of tumor profiling and targeted cancer therapies challenges nurses to keep up-to-date to provide quality patient education and care. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Convergence of Molecular Targets for Cancer Prevention and Therapy

Cancer.gov

Waun Ki Hong, MD, American Cancer Society Professor; Samsung Distinguished University Chair in Cancer Medicine at the University of Texas M. D. Anderson Cancer Center, Houston, TX, presented "Convergence of Molecular Targets for Cancer Prevention and Therapy".

Integration of subclassification strategies in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for non-specific chronic low back pain: a systematic review.

PubMed

Fersum, K V; Dankaerts, W; O'Sullivan, P B; Maes, J; Skouen, J S; Bjordal, J M; Kvåle, A

2010-11-01

There is lack of evidence for specific treatment interventions for patients with non-specific chronic low back pain (NSCLBP) despite the substantial amount of randomised controlled clinical trials evaluating treatment outcome for this disorder. It has been hypothesised that this vacuum of evidence is caused by the lack of subclassification of the heterogeneous population of patients with chronic low back pain for outcome research. A systematic review. A systematic review with a meta-analysis was undertaken to determine the integration of subclassification strategies with matched interventions in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for NSCLBP. A structured search for relevant studies in Embase, Cinahl, Medline, PEDro and the Cochrane Trials Register database, followed by hand searching all relevant studies in English up to December 2008. Only 5 of 68 studies (7.4%) subclassified patients beyond applying general inclusion and exclusion criteria. In the few studies where classification and matched interventions have been used, our meta-analysis showed a statistical difference in favour of the classification-based intervention for reductions in pain (p=0.004) and disability (p=0.0005), both for short-term and long-term reduction in pain (p=0.001). Effect sizes ranged from moderate (0.43) for short term to minimal (0.14) for long term. A better integration of subclassification strategies in NSCLBP outcome research is needed. We propose the development of explicit recommendations for the use of subclassification strategies and evaluation of targeted interventions in future research evaluating NSCLBP.

A view on EGFR-targeted therapies from the oncogene-addiction perspective.

PubMed

Perez, Rolando; Crombet, Tania; de Leon, Joel; Moreno, Ernesto

2013-01-01

Tumor cell growth and survival can often be impaired by inactivating a single oncogen- a phenomenon that has been called as "oncogene addiction." It is in such scenarios that molecular targeted therapies may succeed. among known oncogenes, the epidermal growth factor receptor (EGFR) has become the target of different cancer therapies. So far, however, the clinical benefit from EGFR-targeted therapies has been rather limited. a critical review of the large amount of clinical data obtained with anti-EGFR agents, carried out from the perspective of the oncogene addiction concept, may help to understand the causes of the unsatisfactory results. In this article we intend to do such an exercise taking as basis for the analysis a few case studies of anti-EGFR agents that are currently in the clinic. There, the "EGFR addiction" phenomenon becomes apparent in high-responder patients. We further discuss how the concept of oncogene addiction needs to be interpreted on the light of emerging experimental evidences and ideas; in particular, that EGFR addiction may reflect the interconnection of several cellular pathways. In this regard we set forth several hypotheses; namely, that requirement of higher glucose uptake by hypoxic tumor cells may reinforce EGFR addiction; and that chronic use of EGFR-targeted antibodies in EGFR-addicted tumors would induce stable disease by reversing the malignant phenotype of cancer stem cells and also by sustaining an anti-tumor T cell response. Finally, we discuss possible reasons for the failure of certain combinatorial therapies involving anti-EGFR agents, arguing that some of these agents might produce either a negative or a positive trans-modulation effect on other oncogenes. It becomes evident that we need operational definitions of EGFR addiction in order to determine which patient populations may benefit from treatment with anti-EGFR drugs, and to improve the design of these therapies.

Short- and long-term clinical outcomes following a standardized protocol of orthopedic manual physical therapy and exercise in individuals with osteoarthritis of the hip: a case series.

PubMed

Hando, Ben R; Gill, Norman W; Walker, Michael J; Garber, Mathew

2012-11-01

Describe short- and long-term outcomes observed in individuals with hip osteoarthritis (OA) treated with a pre-selected, standardized set of best-evidence manual therapy and therapeutic exercise interventions. Fifteen consecutive subjects (9 males, 6 females; mean age: 52±7.5 years) with unilateral hip OA received an identical protocol of manual therapy and therapeutic exercise interventions. Subjects attended 10 treatment sessions over an 8-week period for manual therapy interventions and performed the therapeutic exercise as a home program. Baseline to 8-week follow-up outcomes were as follows: Harris Hip Scale (HHS) scores improved from 60.3(±10.4) to 80.7(±10.5), Numerical Pain Rating Scale (NPRS) scores improved from 4.3(±1.9) to 2.0(±1.9), hip flexion range of motion (ROM) improved from 99 degrees (±10.6) to 127 degrees (±6.3) and hip internal rotation ROM improved from 19 degrees (±9.1) to 31 degrees (±11.5). Improvements in HHS, NPRS, and hip ROM measures reached statistical significance (P<0.05) at 8-weeks and remained significant at the 29-week follow-up. Mean changes in NPRS and HHS scores exceeded the minimal clinically important difference (MCID) at 8-weeks and for the HHS scores alone at 29 weeks. The 8 and 29 week mean Global Rating of Change scores were 5.1(±1.4) and 2.1(±4.2), respectively. Improved outcomes observed following a pre-selected, standardized treatment protocol were similar to those observed in previous studies involving impairment-based manual therapy and therapeutic exercise for hip OA. Future studies might directly compare the two approaches.

Targeted exercise therapy for voice and swallow in persons with Parkinson’s disease

PubMed Central

Russell, John A.; Ciucci, Michelle R.; Connor, Nadine P.; Schallert, Timothy

2010-01-01

Sensorimotor deficits affecting voice and swallowing ability can have a devastating impact on the quality of life of people with Parkinson disease (PD). Recent scientific findings in animal models of PD pinpoint targeted exercise therapy as a potential treatment to reduce neurochemical loss and decrease parkinsonian symptoms. Although there may be beneficial effects, targeted exercise therapy is not a standard component of therapy for the cranial sensiromotor deficits seen in PD. In this paper we review the scientific evidence for targeted training for voice and swallowing deficits. The literature search revealed 19 publications that included targeted training for voice and only one publication that included targeted training for swallowing. We summarize 3 main findings: 1) targeted training may be associated with lasting changes in voice behavior, 2) targeted training of sensorimotor actions with anatomical or functional overlap with voice and swallowing may improve voice and swallowing to some degree, but it is unknown whether these effects endure over time, and 3) evidence regarding cranial sensorimotor interventions for Parkinson disease is sparse. We concluded that targeted training for voice and swallow is a promising but under-studied intervention for cranial sensorimotor deficits associated with PD and posit that animal models can be useful in designing empirically based studies that further the science on targeted training. PMID:20233583

Molecular Targeted Drugs and Biomarkers in NSCLC, the Evolving Role of Individualized Therapy

PubMed Central

Domvri, Kalliopi; Zarogoulidis, Paul; Darwiche, Kaid; Browning, Robert F.; Li, Qiang; Turner, J. Francis; Kioumis, Ioannis; Spyratos, Dionysios; Porpodis, Konstantinos; Papaiwannou, Antonis; Tsiouda, Theodora; Freitag, Lutz; Zarogoulidis, Konstantinos

2013-01-01

Lung cancer first line treatment has been directed from the non-specific cytotoxic doublet chemotherapy to the molecular targeted. The major limitation of the targeted therapies still remains the small number of patients positive to gene mutations. Furthermore, the differentiation between second line and maintenance therapy has not been fully clarified and differs in the clinical practice between cancer centers. The authors present a segregation between maintenance treatment and second line and present a possible definition for the term “maintenance” treatment. In addition, cancer cell evolution induces mutations and therefore either targeted therapies or non-specific chemotherapy drugs in many patients become ineffective. In the present work pathways such as epidermal growth factor, anaplastic lymphoma kinase, met proto-oncogene and PI3K are extensively presented and correlated with current chemotherapy treatment. Future, perspectives for targeted treatment are presented based on the current publications and ongoing clinical trials. PMID:24312144

Effects of Mode of Target Task Selection on Learning about Plants in a Mobile Learning Environment: Effortful Manual Selection versus Effortless QR-Code Selection

ERIC Educational Resources Information Center

Gao, Yuan; Liu, Tzu-Chien; Paas, Fred

2016-01-01

This study compared the effects of effortless selection of target plants using quick respond (QR) code technology to effortful manual search and selection of target plants on learning about plants in a mobile device supported learning environment. In addition, it was investigated whether the effectiveness of the 2 selection methods was…

Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

PubMed

Marquet, Pierre; Longeray, Pierre-Henry; Barlesi, Fabrice; Ameye, Véronique; Augé, Pascale; Cazeneuve, Béatrice; Chatelut, Etienne; Diaz, Isabelle; Diviné, Marine; Froguel, Philippe; Goni, Sylvia; Gueyffier, François; Hoog-Labouret, Natalie; Mourah, Samia; Morin-Surroca, Michèle; Perche, Olivier; Perin-Dureau, Florent; Pigeon, Martine; Tisseau, Anne; Verstuyft, Céline

2015-01-01

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Short-term psychodynamic therapy for obsessive-compulsive disorder: A manual-guided approach to treating the "inhibited rebel".

PubMed

Leichsenring, Falk; Steinert, Christiane

2017-01-01

Obsessive-compulsive disorder (OCD) is a chronic disabling disorder characterized by recurrent obsessions and uncontrolled compulsions. Recent research on anxiety disorders suggests that manual-guided short-term psychodynamic therapy (STPP) may be a promising approach. Building on this, a model of STPP for OCD was developed based on Luborsky's supportive-expressive (SE) therapy. Treatment consists of 12 modules, which include the characteristic elements of SE therapy, that is, a focus on the Core Conflictual Relationship Theme (CCRT) associated with OCD symptoms and on establishing a secure alliance. Disorder-specific treatment elements were integrated, including addressing ambivalence, differentiating between thinking and acting, mitigating the superego, addressing existential issues, and, last but not least, implementing Freud's original recommendation to induce OCD patients to face the feared situation and to use the aroused experiences to work on the underlying conflict (i.e., CCRT). There are reasons to assume that the empirically derived model of STPP described here may be beneficial in OCD.

Targeted Therapies in Hematology and Their Impact on Patient Care: Chronic and Acute Myeloid Leukemia

PubMed Central

Cortes, Elias Jabbour Jorge; Ravandi, Farhad; O’Brien, Susan; Kantarjian, Hagop

2014-01-01

Advances in the genetic and molecular characterizations of leukemias have enhanced our capabilities to develop targeted therapies. The most dramatic examples of targeted therapy in cancer to date are the use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) which has revolutionized the treatment of chronic myeloid leukemia (CML). Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. In contrast, acute myeloid leukemia (AML) is an extremely heterogeneous disease with outcomes that vary widely according to subtype of the disease. Targeted therapy with monoclonal antibodies and small molecule kinase inhibitors are promising strategies to help improve the cure rates in AML. In this review, we will highlight the results of recent clinical trials in which outcomes of CML and AML have been influenced significantly. Also, novel approaches to sequencing and combining available therapies will be covered. PMID:24246694

Gene therapy to target ER stress in brain diseases.

PubMed

Valenzuela, Vicente; Martínez, Gabriela; Duran-Aniotz, Claudia; Hetz, Claudio

2016-10-01

Gene therapy based on the use of Adeno-associated viruses (AAVs) is emerging as a safe and stable strategy to target molecular pathways involved in a variety of brain diseases. Endoplasmic reticulum (ER) stress is proposed as a transversal feature of most animal models and clinical samples from patients affected with neurodegenerative diseases. Manipulation of the unfolded protein response (UPR), a major homeostatic reaction under ER stress conditions, had proved beneficial in diverse models of neurodegeneration. Although increasing number of drugs are available to target ER stress, the use of small molecules to treat chronic brain diseases is challenging because of poor blood brain barrier permeability and undesirable side effects due to the role of the UPR in the physiology of peripheral organs. Gene therapy is currently considered a possible future alternative to circumvent these problems by the delivery of therapeutic agents to selective regions and cell types of the nervous system. Here we discuss current efforts to design gene therapy strategies to alleviate ER stress on a disease context. This article is part of a Special Issue entitled SI:ER stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-VEGF/VEGFR therapy for cancer: reassessing the target.

PubMed

Sitohy, Basel; Nagy, Janice A; Dvorak, Harold F

2012-04-15

Judah Folkman recognized that new blood vessel formation is important for tumor growth and proposed antiangiogenesis as a novel approach to cancer therapy. Discovery of vascular permeability factor VEGF-A as the primary tumor angiogenesis factor prompted the development of a number of drugs that targeted it or its receptors. These agents have often been successful in halting tumor angiogenesis and in regressing rapidly growing mouse tumors. However, results in human cancer have been less impressive. A number of reasons have been offered for the lack of greater success, and, here, we call attention to the heterogeneity of the tumor vasculature as an important issue. Human and mouse tumors are supplied by at least 6 well-defined blood vessel types that arise by both angiogenesis and arterio-venogenesis. All 6 types can be generated in mouse tissues by an adenoviral vector expressing VEGF-A(164). Once formed, 4 of the 6 types lose their VEGF-A dependency, and so their responsiveness to anti-VEGF/VEGF receptor therapy. If therapies directed against the vasculature are to have a greater impact on human cancer, targets other than VEGF and its receptors will need to be identified on these resistant tumor vessels.

Mutation testing for directing upfront targeted therapy and post-progression combination therapy strategies in lung adenocarcinoma

PubMed Central

Salgia, Ravi

2016-01-01

ABSTRACT Introduction: Advances in the biology of non-small-cell lung cancer, especially adenocarcinoma, reveal multiple molecular subtypes driving oncogenesis. Accordingly, individualized targeted therapeutics are based on mutational diagnostics. Areas covered: Advances in strategies and techniques for individualized treatment, particularly of adenocarcinoma, are described through literature review. Approved therapies are established for some molecular subsets, with new driver mutations emerging that represent increasing proportions of patients. Actionable mutations are de novo oncogenic drivers or acquired resistance mediators, and mutational profiling is important for directing therapy. Patients should be monitored for emerging actionable resistance mutations. Liquid biopsy and associated multiplex diagnostics will be important means to monitor patients during treatment. Expert commentary: Outcomes with targeted agents may be improved by integrating mutation screens during treatment to optimize subsequent therapy. In order for this to be translated into impactful patient benefit, appropriate platforms and strategies need to be optimized and then implemented universally. PMID:27139190

Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

PubMed

Distler, Oliver; Cozzio, Antonio

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

A perspective on B-cell-targeting therapy for SLE.

PubMed

Looney, R John; Anolik, Jennifer; Sanz, Inaki

2010-02-01

In recent years, large controlled trials have tested several new agents for systemic lupus erythematosus (SLE). Unfortunately, none of these trials has met its primary outcome. This does not mean progress has not been made. In fact, a great deal has been learned about doing clinical trials in lupus and about the biological and clinical effects of the drugs being tested. Many of these drugs were designed to target B cells directly, e.g., rituximab, belimumab, epratuzumab, and transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig). The enthusiasm for targeting B cells derives from substantial evidence showing the critical role of B cells in murine models of SLE, as well promising results from multiple open trials with rituximab, a chimeric anti-CD20 monoclonal antibody that specifically depletes B cells (Martin and Chan in Immunity 20(5):517-527, 2004; Sobel et al. in J Exp Med 173:1441-1449, 1991; Silverman and Weisman in Arthritis Rheum 48:1484-1492, 2003; Silverman in Arthritis Rheum 52(4):1342, 2005; Shlomchik et al. in Nat Rev Immunol 1:147-153, 2001; Looney et al. in Arthritis Rheum 50:2580-2589, 2004; Lu et al. in Arthritis Rheum 61(4):482-487, 2009; Saito et al. in Lupus 12(10):798-800, 2003; van Vollenhoven et al. in Scand J Rheumatol 33(6):423-427, 2004; Sfikakis et al. Arthritis Rheum 52(2):501-513, 2005). Why have the controlled trials of B-cell-targeting therapies failed to demonstrate efficacy? Were there flaws in design or execution of these trials? Or, were promising animal studies and open trials misleading, as so often happens? This perspective discusses the current state of B-cell-targeting therapies for human lupus and the future development of these therapies.

Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

PubMed Central

Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

2014-01-01

There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy

PubMed Central

Javan, Bita; Shahbazi, Majid

2017-01-01

Transcriptional targeting is the best approach for specific gene therapy. Hypoxia is a common feature of the tumour microenvironment. Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. However, this system needs to be optimised to have maximum efficacy with minimum side effects in normal tissues. The combination of tissue-/tumour-specific promoters with HRE core sequences has been found to enhance the specificity and efficacy of this system. In this review, hypoxia-inducible gene expression system as well as gene therapy strategies targeting tumour hypoxia will be discussed. This review will also focus on hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation systems developed for cancer-specific gene therapy. PMID:28798809

Targeted Antiangiogenesis Gene Therapy Using Targeted Cationic Microbubbles Conjugated with CD105 Antibody Compared with Untargeted Cationic and Neutral Microbubbles

PubMed Central

Zhou, Yu; Gu, Haitao; Xu, Yan; Li, Fan; Kuang, Shaojing; Wang, Zhigang; Zhou, Xiyuan; Ma, Huafeng; Li, Pan; Zheng, Yuanyi; Ran, Haitao; Jian, Jia; Zhao, Yajing; Song, Weixiang; Wang, Qiushi; Wang, Dong

2015-01-01

Objective This study aimed to develop targeted cationic microbubbles conjugated with a CD105 antibody (CMB105) for use in targeted vascular endothelial cell gene therapy and ultrasound imaging. We compared the results with untargeted cationic microbubbles (CMB) and neutral microbubbles (NMB). Methods CMB105 were prepared and compared with untargeted CMB and NMB. First, the microbubbles were characterized in terms of size, zeta-potential, antibody binding ability and plasmid DNA loading capacity. A tumor model of subcutaneous breast cancer in nude mice was used for our experiments. The ability of different types of microbubbles to target HUVECs in vitro and tumor neovascularization in vivo was measured. The endostatin gene was selected for its outstanding antiangiogenesis effect. For in vitro experiments, the transfection efficiency and cell cycle were analyzed using flow cytometry, and the transcription and expression of endostatin were measured by qPCR and Western blotting, respectively. Vascular tube cavity formation and tumor cell invasion were used to evaluate the antiangiogenesis gene therapy efficiency in vitro. Tumors were exposed to ultrasound irradiation with different types of microbubbles, and the gene therapy effects were investigated by detecting apoptosis induction and changes in tumor volume. Results CMB105 and CMB differed significantly from NMB in terms of zeta-potential, and the DNA loading capacities were 16.76±1.75 μg, 18.21±1.22 μg, and 0.48±0.04 μg per 5×108 microbubbles, respectively. The charge coupling of plasmid DNA to CMB105 was not affected by the presence of the CD105 antibody. Both CMB105 and CMB could target to HUVECs in vitro, whereas only CMB105 could target to tumor neovascularization in vivo. In in vitro experiments, the transfection efficiency of CMB105 was 24.7-fold higher than the transfection efficiency of NMB and 1.47-fold higher than the transfection efficiency of CMB (P<0.05). With ultrasound-targeted microbubble

Targeted antiangiogenesis gene therapy using targeted cationic microbubbles conjugated with CD105 antibody compared with untargeted cationic and neutral microbubbles.

PubMed

Zhou, Yu; Gu, Haitao; Xu, Yan; Li, Fan; Kuang, Shaojing; Wang, Zhigang; Zhou, Xiyuan; Ma, Huafeng; Li, Pan; Zheng, Yuanyi; Ran, Haitao; Jian, Jia; Zhao, Yajing; Song, Weixiang; Wang, Qiushi; Wang, Dong

2015-01-01

This study aimed to develop targeted cationic microbubbles conjugated with a CD105 antibody (CMB105) for use in targeted vascular endothelial cell gene therapy and ultrasound imaging. We compared the results with untargeted cationic microbubbles (CMB) and neutral microbubbles (NMB). CMB105 were prepared and compared with untargeted CMB and NMB. First, the microbubbles were characterized in terms of size, zeta-potential, antibody binding ability and plasmid DNA loading capacity. A tumor model of subcutaneous breast cancer in nude mice was used for our experiments. The ability of different types of microbubbles to target HUVECs in vitro and tumor neovascularization in vivo was measured. The endostatin gene was selected for its outstanding antiangiogenesis effect. For in vitro experiments, the transfection efficiency and cell cycle were analyzed using flow cytometry, and the transcription and expression of endostatin were measured by qPCR and Western blotting, respectively. Vascular tube cavity formation and tumor cell invasion were used to evaluate the antiangiogenesis gene therapy efficiency in vitro. Tumors were exposed to ultrasound irradiation with different types of microbubbles, and the gene therapy effects were investigated by detecting apoptosis induction and changes in tumor volume. CMB105 and CMB differed significantly from NMB in terms of zeta-potential, and the DNA loading capacities were 16.76±1.75 μg, 18.21±1.22 μg, and 0.48±0.04 μg per 5×10(8) microbubbles, respectively. The charge coupling of plasmid DNA to CMB105 was not affected by the presence of the CD105 antibody. Both CMB105 and CMB could target to HUVECs in vitro, whereas only CMB105 could target to tumor neovascularization in vivo. In in vitro experiments, the transfection efficiency of CMB105 was 24.7-fold higher than the transfection efficiency of NMB and 1.47-fold higher than the transfection efficiency of CMB (P<0.05). With ultrasound-targeted microbubble destruction (UTMD

Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted therapy.

PubMed

Zhan, Changyou; Li, Chong; Wei, Xiaoli; Lu, Wuyuan; Lu, Weiyue

2015-08-01

Protein and peptide toxins offer an invaluable source for the development of actively targeted drug delivery systems. They avidly bind to a variety of cognate receptors, some of which are expressed or even up-regulated in diseased tissues and biological barriers. Protein and peptide toxins or their derivatives can act as ligands to facilitate tissue- or organ-specific accumulation of therapeutics. Some toxins have evolved from a relatively small number of structural frameworks that are particularly suitable for addressing the crucial issues of potency and stability, making them an instrumental source of leads and templates for targeted therapy. The focus of this review is on protein and peptide toxins for the development of targeted drug delivery systems and molecular therapies. We summarize disease- and biological barrier-related toxin receptors, as well as targeted drug delivery strategies inspired by those receptors. The design of new therapeutics based on protein and peptide toxins is also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeted Therapies for Advanced Oesophagogastric Cancer: Recent Progress and Future Directions.

PubMed

Young, Kate; Chau, Ian

2016-01-01

The genomic landscape of oesophagogastric (OG) cancer is highly complex. The recent elucidation of some of the pathways involved has suggested a number of novel targets for therapy. This therapy is urgently required as with conventional chemotherapy regimens patients with advanced OG cancer still have a median overall survival of under a year. This review outlines the rationale for the current treatment of OG cancer with chemotherapy and describes both previously conducted and ongoing clinical trials of novel agents in this area. The targets and associated treatments discussed include HER-2, EGFR, VEGF, c-Met, FGFR-2, PI3K, mTOR andIGF-1. To date only two targeted treatments, trastuzumab and ramucirumab, have become part of the treatment paradigm for OG cancer, partly due to difficulties in defining predictive biomarkers in this disease. However, there are a number of promising drugs in the pipeline and this article seeks to describe these and other potential novel approaches including targeting DNA repair deficiencies and the immune system.

Do Subjects with Whiplash-Associated Disorders Respond Differently in the Short-Term to Manual Therapy and Exercise than Those with Mechanical Neck Pain?

PubMed

Castaldo, Matteo; Catena, Antonella; Chiarotto, Alessandro; Fernández-de-Las-Peñas, César; Arendt-Nielsen, Lars

2017-04-01

To compare the short-term effects of manual therapy and exercise on pain, related disability, range of motion, and pressure pain thresholds between subjects with mechanical neck pain and whiplash-associated disorders. Twenty-two subjects with mechanical neck pain and 28 with whiplash-associated disorders participated. Clinical and physical outcomes including neck pain intensity, neck-related disability, and pain area, as well as cervical range of motion and pressure pain thresholds over the upper trapezius and tibialis anterior muscles, were obtained at baseline and after the intervention by a blinded assessor. Each subject received six sessions of manual therapy and specific neck exercises. Mixed-model repeated measures analyses of covariance (ANCOVAs) were used for the analyses. Subjects with whiplash-associated disorders exhibited higher neck-related disability ( P  = 0.021), larger pain area ( P  = 0.003), and lower pressure pain thresholds in the tibialis anterior muscle ( P  = 0.009) than those with mechanical neck pain. The adjusted ANCOVA revealed no between-group differences for any outcome (all P  > 0.15). A significant main effect of time was demonstrated for clinical outcomes and cervical range of motion with both groups experiencing similar improvements (all P  < 0.01). No changes in pressure pain thresholds were observed in either group after treatment ( P  > 0.222). The current clinical trial found that subjects with mechanical neck pain and whiplash-associated disorders exhibited similar clinical and neurophysiological responses after a multimodal physical therapy intervention, suggesting that although greater signs of central sensitization are present in subjects with whiplash-associated disorders, this does not alter the response in the short term to manual therapy and exercises. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study.

PubMed

Walker, Jochen; Mertens, Ulf Kai; Schmidt, Carsten Oliver; Chenot, Jean-François

2017-01-01

Spinal manual therapy (SMT) is a popular treatment option for low back pain (LBP). The aim of our analysis was to evaluate the effects of manual therapy delivered by general practitioners and ambulatory orthopedic surgeons in routine care on follow up consultations, sick leave, health service utilization and costs for acute LBP compared to matched patients not receiving manual therapy. This is a propensity score matched cohort study based on health claims data. We identified a total of 113.652 adult patients with acute LBP and no coded red flags of whom 21.021 (18%) received SMT by physicians. In the final analysis 17.965 patients in each group could be matched. Balance on patients' coded characteristics, comorbidity and prior health service utilization was achieved. The provision of SMT for acute LBP had no relevant impact on follow up visits and days of sick leave for LBP in the index billing period and the following year. SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs. 23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by replacing other health services for LBP. SMT for acute non-specific LBP in routine care was not clinically meaningful effective to reduce sick leave and reconsultation rates compared to no SMT and did not lead to meaningful savings by replacing other health services from the perspective of health insurance. This does not imply that SMT is ineffective but might reflect a problem with selection of suitable patients and the quality and quantity of SMT in routine care. National Manual Medicine societies should state clearly that imaging is not routinely needed prior to SMT in patients with low suspicion of presence of red flags and monitor the quality of provided services.

Common Manual Therapy Practices in the Netherlands for Infants With Upper Cervical Dysfunction: A Prospective Cohort Study.

PubMed

Saedt, Eric R I C; Driehuis, Femke; Hoogeboom, Thomas J; van der Woude, Bé H; de Bie, Rob A; Nijhuis-van der Sanden, Maria W G

2018-01-01

The purpose of this study was to describe common clinical practices of manual therapists (MTs) in the Netherlands for infants with indications of upper cervical dysfunction (UCD). A prospective observational cohort study was conducted to gain insight into characteristics, reasons for seeking care, and common clinical practice for infants (<27 weeks) with indications of UCD, referred to MTs. Pre- and posttreatment self-reported questionnaires were used to collect data from parents and MTs. Parents reported on infant characteristics and perceived effect of treatment. Manual therapists reported on diagnostics, therapeutic procedures, and outcomes. Between 2006 and 2007, data regarding 307 referred infants (mean age: 11.2 weeks) were collected by parents and 42 MTs. The most frequent reasons for seeking care were positional preference, restlessness, and/or abnormal head position. Manual therapists observed active, spontaneous, and provoked mobility and passive upper cervical mobility. Of the 307 infants, 295 were diagnosed with UCD based on positive outcomes on the flexion-rotation test and/or lateral flexion test. After treatment with mobilization techniques, positive outcomes on the flexion-rotation test decreased from 78.8% to 6.8%. For the lateral flexion test, the positive outcomes decreased from 91.5% to 6.2%. All parents perceived positive treatment effects. No serious adverse events were reported during this study. This is the first study to describe common clinical practice for infants referred for manual therapy. Infants with UCD were treated mainly with upper cervical mobilization techniques, and the greatest perceived effect was observed after approximately 2 treatment sessions. Copyright © 2018. Published by Elsevier Inc.

Molecularly-Targeted Gold-Based Nanoparticles for Cancer Imaging and Near-Infrared Photothermal Therapy

NASA Astrophysics Data System (ADS)

Day, Emily Shannon

2011-12-01

This thesis advances the use of nanoparticles as multifunctional agents for molecularly-targeted cancer imaging and photothermal therapy. Cancer mortality has remained relatively unchanged for several decades, indicating a significant need for improvements in care. Researchers are evaluating strategies incorporating nanoparticles as exogenous energy absorbers to deliver heat capable of inducing cell death selectively to tumors, sparing normal tissue. Molecular targeting of nanoparticles is predicted to improve photothermal therapy by enhancing tumor retention. This hypothesis is evaluated with two types of nanoparticles. The nanoparticles utilized, silica-gold nanoshells and gold-gold sulfide nanoparticles, can convert light energy into heat to damage cancerous cells. For in vivo applications nanoparticles are usually coated with poly(ethylene glycol) (PEG) to increase blood circulation time. Here, heterobifunctional PEG links nanoparticles to targeting agents (antibodies and growth factors) to provide cell-specific binding. This approach is evaluated through a series of experiments. In vitro, antibody-coated nanoparticles can bind breast carcinoma cells expressing the targeted receptor and act as contrast agents for multiphoton microscopy prior to inducing cell death via photoablation. Furthermore, antibody-coated nanoparticles can bind tissue ex vivo at levels corresponding to receptor expression, suggesting they should bind their target even in the complex biological milieu. This is evaluated by comparing the accumulation of antibody-coated and PEG-coated nanoparticles in subcutaneous glioma tumors in mice. Contrary to expectations, antibody targeting did not yield more nanoparticles within tumors. Nevertheless, these studies established the sensitivity of glioma to photothermal therapy; mice treated with PEG-coated nanoshells experienced 57% complete tumor regression versus no regression in control mice. Subsequent experiments employed intracranial tumors to

Microbiota-targeted therapies on the intensive care unit.

PubMed

Haak, Bastiaan W; Levi, Marcel; Wiersinga, W Joost

2017-04-01

The composition and diversity of the microbiota of the human gut, skin, and several other sites is severely deranged in critically ill patients on the ICU, and it is likely that these disruptions can negatively affect outcome. We here review new and ongoing studies that investigate the use of microbiota-targeted therapeutics in the ICU, and provide recommendations for future research. Practically every intervention in the ICU as well as the physiological effects of critical illness itself can have a profound impact on the gut microbiota. Therapeutic modulation of the microbiota, aimed at restoring the balance between 'pathogenic' and 'health-promoting' microbes is therefore of significant interest. Probiotics have shown to be effective in the treatment of ventilator-associated pneumonia, and the first fecal microbiota transplantations have recently been safely and successfully performed in the ICU. However, all-encompassing data in this vulnerable patient group remain sparse, and only a handful of novel studies that study microbiota-targeted therapies in the ICU are currently ongoing. Enormous strides have been made in characterizing the gut microbiome of critically ill patients in the ICU, and an increasing amount of preclinical data reveals the huge potential of microbiota-targeted therapies. Further understanding of the causes and consequences of dysbiosis on ICU-related outcomes are warranted to push the field forward.

Temozolomide nanoparticles for targeted glioblastoma therapy.

PubMed

Fang, Chen; Wang, Kui; Stephen, Zachary R; Mu, Qingxin; Kievit, Forrest M; Chiu, Daniel T; Press, Oliver W; Zhang, Miqin

2015-04-01

Glioblastoma (GBM) is a deadly and debilitating brain tumor with an abysmal prognosis. The standard therapy for GBM is surgery followed by radiation and chemotherapy with Temozolomide (TMZ). Treatment of GBMs remains a challenge, largely because of the fast degradation of TMZ, the inability to deliver an effective dose of TMZ to tumors, and a lack of target specificity that may cause systemic toxicity. Here, we present a simple method for synthesizing a nanoparticle-based carrier that can protect TMZ from rapid degradation in physiological solutions and can specifically deliver them to GBM cells through the mediation of a tumor-targeting peptide chlorotoxin (CTX). Our nanoparticle, namely NP-TMZ-CTX, had a hydrodynamic size of <100 nm, exhibited sustained stability in cell culture media for up to 2 weeks, and could accommodate stable drug loading. TMZ bound to nanoparticles showed a much higher stability at physiological pH, with a half-life 7-fold greater than that of free TMZ. NP-TMZ-CTX was able to target GBM cells and achieved 2-6-fold higher uptake and a 50-90% reduction of IC50 72 h post-treatment as compared to nontargeted NP-TMZ. NP-TMZ-CTX showed great promise in its ability to deliver a large therapeutic dose of TMZ to GBM cells and could serve as a template for targeted delivery of other therapeutics.

Novel Targeted Therapies for Inflammatory Bowel Disease.

PubMed

Coskun, Mehmet; Vermeire, Severine; Nielsen, Ole Haagen

2017-02-01

Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easily administered therapeutics that may be viable candidates for the management of IBD, such as antibodies against interleukin 6 (IL-6) and IL-12/23, small molecules including Janus kinase inhibitors, antisense oligonucleotide against SMAD7 mRNA, and inhibitors of leukocyte trafficking to intestinal sites of inflammation (e.g., sphingosine 1-phosphate receptor modulators). We also provide an update on the current status in clinical development of these new classes of therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel medical therapeutics in glioblastomas, including targeted molecular therapies, current and future clinical trials.

PubMed

Quant, Eudocia C; Wen, Patrick Y

2010-08-01

The prognosis for glioblastoma is poor despite optimal therapy with surgery, radiation, and chemotherapy. New therapies that improve survival and quality of life are needed. Research has increased our understanding of the molecular pathways important for gliomagenesis and disease progression. Novel agents have been developed against these targets, including receptor tyrosine kinases, intracellular signaling molecules, epigenetic abnormalities, and tumor vasculature and microenvironment. This article reviews novel therapies for glioblastoma, with an emphasis on targeted agents. Copyright 2010 Elsevier Inc. All rights reserved.

Targeted drug delivery for cancer therapy: the other side of antibodies

PubMed Central

2012-01-01

Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs), particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients. PMID:23140144

Short- and long-term clinical outcomes following a standardized protocol of orthopedic manual physical therapy and exercise in individuals with osteoarthritis of the hip: a case series

PubMed Central

Hando, Ben R; Gill, Norman W; Walker, Michael J; Garber, Mathew

2012-01-01

Objectives: Describe short- and long-term outcomes observed in individuals with hip osteoarthritis (OA) treated with a pre-selected, standardized set of best-evidence manual therapy and therapeutic exercise interventions. Methods: Fifteen consecutive subjects (9 males, 6 females; mean age: 52±7.5 years) with unilateral hip OA received an identical protocol of manual therapy and therapeutic exercise interventions. Subjects attended 10 treatment sessions over an 8-week period for manual therapy interventions and performed the therapeutic exercise as a home program. Results: Baseline to 8-week follow-up outcomes were as follows: Harris Hip Scale (HHS) scores improved from 60.3(±10.4) to 80.7(±10.5), Numerical Pain Rating Scale (NPRS) scores improved from 4.3(±1.9) to 2.0(±1.9), hip flexion range of motion (ROM) improved from 99 degrees (±10.6) to 127 degrees (±6.3) and hip internal rotation ROM improved from 19 degrees (±9.1) to 31 degrees (±11.5). Improvements in HHS, NPRS, and hip ROM measures reached statistical significance (P<0.05) at 8-weeks and remained significant at the 29-week follow-up. Mean changes in NPRS and HHS scores exceeded the minimal clinically important difference (MCID) at 8-weeks and for the HHS scores alone at 29 weeks. The 8 and 29 week mean Global Rating of Change scores were 5.1(±1.4) and 2.1(±4.2), respectively. Improved outcomes observed following a pre-selected, standardized treatment protocol were similar to those observed in previous studies involving impairment-based manual therapy and therapeutic exercise for hip OA. Future studies might directly compare the two approaches. Discussion: PMID:24179327

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

PubMed

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma.

PubMed

Kozakiewicz, Paulina; Grzybowska-Szatkowska, Ludmiła

2018-05-01

Despite the development of standard therapies, including surgery, radiotherapy and chemotherapy, survival rates for head and neck squamous cell carcinoma (HNSCC) have not changed significantly over the past three decades. Complete recovery is achieved in <50% of patients. The treatment of advanced HNSCC frequently requires multimodality therapy and involves significant toxicity. The promising, novel treatment option for patients with HNSCC is molecular-targeted therapies. The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib), vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or vascular endothelial growth factor receptor (VEGFR) inhibitors (sorafenib, sunitinib and vandetanib) and inhibitors of phosphatidylinositol 3-kinase/serine/threonine-specific protein kinase/mammalian target of rapamycin. There are also various inhibitors of other pathways and targets, which are promising and require evaluation in further studies.

A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

PubMed

Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

2014-04-01

The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

Dual-Responsive Molecular Probe for Tumor Targeted Imaging and Photodynamic Therapy

PubMed Central

Meng, Xiaoqing; Yang, Yueting; Zhou, Lihua; Zhang, li; Lv, Yalin; Li, Sanpeng; Wu, Yayun; Zheng, Mingbin; Li, Wenjun; Gao, Guanhui; Deng, Guanjun; Jiang, Tao; Ni, Dapeng; Gong, Ping; Cai, Lintao

2017-01-01

The precision oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging and therapeutics. In this study, a first small-molecule theranostic probe, RhoSSCy is constructed by conjugating 5′-carboxyrhodamines (Rho) and heptamethine cyanine IR765 (Cy) using a reducible disulfide linker and pH tunable amino-group to realize thiols/pH dual sensing. In vitro experiments verify that RhoSSCy is highly sensitive for quantitative analysis and imaging intracellular pH gradient and biothiols. Furthermore, RhoSSCy shows superb tumor targeted dual-modal imaging via near-infrared fluorescence (NIRF) and photoacoustic (PA). Importantly, RhoSSCy also induces strongly reactive oxygen species for tumor photodynamic therapy (PDT) with robust antitumor activity both in vitro and in vivo. Such versatile small-molecule theranostic probe may be promising for tumor targeted imaging and precision therapy. PMID:28638467

Therapies targeting cancer stem cells: Current trends and future challenges

PubMed Central

Dragu, Denisa L; Necula, Laura G; Bleotu, Coralia; Diaconu, Carmen C; Chivu-Economescu, Mihaela

2015-01-01

Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells (CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a long-lasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of miRNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers. PMID:26516409

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies.

PubMed

Ransohoff, Julia D; Kwong, Bernice Y

2017-12-01

The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies. We systematically review according to drug-targeting pathway the cutaneous AE profiles of these drugs, and offer insight when possible into whether pharmacologic target versus immunologic modulation primarily underlie presentation. We include discussion of tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib), blinatumomab, ibrutinib, idelalisib, anti-B cell antibodies (rituximab, ibritumomab, obinutuzumab, ofatumumab, tositumomab), immune checkpoint inhibitors (nivolumab, pembrolizumab), alemtuzumab, brentuximab, and proteasome inhibitors (bortezomib, carfilzomib, ixazomib). We highlight skin reactions seen with antiliquid but not solid tumor agents, draw attention to serious cutaneous AEs that might require therapy modification or cessation, and offer management strategies to permit treatment tolerability. We emphasize the importance of early diagnosis and treatment to minimize disruptions to care, optimize prognosis and quality of life, and promptly address life-threatening skin or infectious events. This evolving partnership between oncologists and dermatologists in the iterative characterization and management of skin toxicities will contribute to a better understanding of these drugs' cutaneous targets and improved patient care. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting STATs for cancer therapy: "Undruggable" no more.

PubMed

Frank, David A

2012-10-01

We are in the midst of an exciting transition in the treatment of cancers, from the empirically developed non-specifically cytotoxic drugs to the era of rationally derived molecularly targeted therapies. Over the past 15 years, our understanding of the mutations that drive cancer pathogenesis has grown enormously, which has rapidly led to the development of drugs to target the associated gene products. Almost all of this focus has been on kinases, largely tyrosine kinases that are activated by translocations, point mutations, insertions and deletions. Although this approach will continue to bear fruit for some time, there is increasing evidence that the returns will be diminishing. First, dominant activating mutations in kinases are less frequent then initially expected particularly in common human cancers, and thus the number of patient whose tumors have suitable targets may be limited. The second cause for concern is the rapid development of resistance that often occurs, arising either from mutations in the target kinase or activation of a parallel pathway. Thus, the desire to target a common convergence point of multiple pathways that directly contributes to the oncogenic phenotype is highly desirable. This goal has led to consideration of transcription factors as therapeutic targets.

Closed-loop assisted versus manual goal-directed fluid therapy during high-risk abdominal surgery: a case-control study with propensity matching.

PubMed

Rinehart, Joseph; Lilot, Marc; Lee, Christine; Joosten, Alexandre; Huynh, Trish; Canales, Cecilia; Imagawa, David; Demirjian, Aram; Cannesson, Maxime

2015-03-19

Goal-directed fluid therapy strategies have been shown to benefit moderate- to high-risk surgery patients. Despite this, these strategies are often not implemented. The aim of this study was to assess a closed-loop fluid administration system in a surgical cohort and compare the results with those for matched patients who received manual management. Our hypothesis was that the patients receiving closed-loop assistance would spend more time in a preload-independent state, defined as percentage of case time with stroke volume variation less than or equal to 12%. Patients eligible for the study were all those over 18 years of age scheduled for hepatobiliary, pancreatic or splenic surgery and expected to receive intravascular arterial blood pressure monitoring as part of their anesthetic care. The closed-loop resuscitation target was selected by the primary anesthesia team, and the system was responsible for implementation of goal-directed fluid therapy during surgery. Following completion of enrollment, each study patient was matched to a non-closed-loop assisted case performed during the same time period using a propensity match to reduce bias. A total of 40 patients were enrolled, 5 were ultimately excluded and 25 matched pairs were selected from among the remaining 35 patients within the predefined caliper distance. There was no significant difference in fluid administration between groups. The closed-loop group spent a significantly higher portion of case time in a preload-independent state (95 ± 6% of case time versus 87 ± 14%, P =0.008). There was no difference in case mean or final stroke volume index (45 ± 10 versus 43 ± 9 and 45 ± 11 versus 42 ± 11, respectively) or mean arterial pressure (79 ± 8 versus 83 ± 9). Case end heart rate was significantly lower in the closed-loop assisted group (77 ± 10 versus 88 ± 13, P =0.003). In this case-control study with propensity matching, clinician use of closed

Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov.

PubMed

Xu, Jun; Lee, Hee-Jin; Zeng, Jia; Wu, Yonghui; Zhang, Yaoyun; Huang, Liang-Chin; Johnson, Amber; Holla, Vijaykumar; Bailey, Ann M; Cohen, Trevor; Meric-Bernstam, Funda; Bernstam, Elmer V; Xu, Hua

2016-07-01

Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

EXERCISE, MANUAL THERAPY AND POSTURAL RE-EDUCATION FOR UNCONTROLLED EAR TWITCHING AND RELATED IMPAIRMENTS AFTER WHIPLASH INJURY: A CASE REPORT.

PubMed

Flanders, Kelsey; Feldner, Heather

2017-10-01

Whiplash Associated Disorders and the interventions used to remediate them are well documented in physical therapy literature. However, specific interventions for spasms of the neck musculature that also involve constant ear twitching have yet to be addressed. The purpose of this case report is twofold. First, to describe comprehensive physical therapy management and outcomes for a subject with uncontrolled ear twitching and related musculoskeletal impairments, and second, to discuss the physical therapist's approach to evidence-based care when faced with a paucity of literature addressing physical therapy interventions for subjects with uncontrolled ear twitching. The subject was a 14-year-old female who sustained a right anterolateral whiplash injury when struck in the head by a volleyball seven months prior to physical therapy. Beginning five months after that injury, she experienced uncontrolled and constant superior/inferior movement of her right ear (hereafter described in this report as a twitch) in addition to facial and cervical pain from her initial injury. She was unable to participate in high school athletics due to her pain. A multimodal treatment approach including exercise, manual therapy, and postural reeducation was utilized during the subject's episode of care. After eight treatment sessions, the subjects's cervical range of motion and upper extremity strength improved. The reported frequency of ear twitching decreased, as did reports of neck and shoulder pain. In addition, her Neck Disability Index improved from a score of 22, indicating moderate disability, to 9, indicating mild disability and she was able to return to sport activity. With limited research to direct intervention, clinical reasoning was utilized to formulate an effective therapeutic intervention. A combination of manual therapy, exercise, and postural reeducation intervention was effective for this subject and could assist in guiding interventions for similarly unique clinical

Anti-VEGF/VEGFR therapy for cancer: Reassessing the target

PubMed Central

Sitohy, Basel; Nagy, Janice A.; Dvorak, Harold F.

2012-01-01

Judah Folkman recognized that new blood vessel formation is important for tumor growth and proposed anti-angiogenesis as a novel approach to cancer therapy. Discovery of vascular permeability factor/vascular endothelial growth factor (VEGF-A) as the primary tumor angiogenesis factor prompted the development of a number of drugs that targeted it or its receptors. These agents have often been successful in halting tumor angiogenesis and in regressing rapidly growing mouse tumors. However, results in human cancer have been less impressive. A number of reasons have been offered for the lack of greater success, and we here call attention to the heterogeneity of the tumor vasculature as an important issue. Human and mouse tumors are supplied by at least six well-defined blood vessel types that arise by both angiogenesis and arterio-venogenesis. All six types can be generated in mouse tissues by an adenoviral vector expressing VEGF-A164. Once formed, four of the six types lose their VEGF-A dependency and so their responsiveness to anti-VEGF/VEGFR therapy. If therapies directed against the vasculature are to have a greater impact on human cancer, targets other than VEGF and its receptors will need to be identified on these resistant tumor vessels. PMID:22508695

Do manual therapy techniques have a positive effect on quality of life in people with tension-type headache? A randomized controlled trial.

PubMed

Espí-López, Gemma V; Rodríguez-Blanco, Cleofás; Oliva-Pascual-Vaca, Angel; Molina-Martínez, Francisco; Falla, Deborah

2016-08-01

Controversy exists regarding the effectiveness of manual therapy for the relief of tension-type headache (TTH). However most studies have addressed the impact of therapy on the frequency and intensity of pain. No studies have evaluated the potentially significant effect on the patient's quality of life. To assess the quality of life of patients suffering from TTH treated for 4 weeks with different manual therapy techniques. Factorial, randomized, single-blinded, controlled clinical trial. Specialized center for the treatment of headache. Seventy-six (62 women) patients aged between 18 and 65 years (age: 39.9±10.9) with either episodic or chronic TTH. Patients were divided into four groups: suboccipital inhibitory pressure; suboccipital spinal manipulation; a combination of the two treatments; control. Quality of life was assessed using the SF-12 questionnaire (considering both the overall score and the different dimensions) at the beginning and end of treatment, and after a one month follow-up. Compared to baseline, the suboccipital inhibition treatment group showed a significant improvement in their overall quality of life at the one month follow-up and also showed specific improvement in the dimensions related to moderate physical activities, and in their emotional role. All the treatment groups, but not the control group, showed improvements in their physical role, bodily pain, and social functioning at the one month follow-up. Post treatment and at the one month follow-up, the combined treatment group showed improved vitality and the two treatment groups that involved manipulation showed improved mental health. All three treatments were effective at changing different dimensions of quality of life, but the combined treatment showed the most change. The results support the effectiveness of treatments applied to the suboccipital region for patients with TTH. Manual therapy techniques applied to the suboccipital region, for as little as four weeks, offered a

Dissociated effects of distractors on saccades and manual aiming.

PubMed

McIntosh, Robert D; Buonocore, Antimo

2012-08-01

The remote distractor effect (RDE) is a robust phenomenon whereby target-directed saccades are delayed by the appearance of a distractor. This effect persists even when the target location is perfectly predictable. The RDE has been studied extensively in the oculomotor domain but it is unknown whether it generalises to other spatially oriented responses. In three experiments, we tested whether the RDE generalises to manual aiming. Experiment 1 required participants to move their hand or eyes to predictable targets presented alone or accompanied by a distractor in the opposite hemifield. The RDE was observed for the eyes but not for the hand. Experiment 2 replicated this dissociation in a more naturalistic task in which eye movements were not constrained during manual aiming. Experiment 3 confirmed the lack of manual RDE across a wider range of distractor delays (0, 50, 100, and 150 ms). Our data imply that the RDE is specific to the oculomotor system, at least for non-foveal distractors. We suggest that the oculomotor RDE reflects competitive interactions between target and distractor representations in the superior colliculus, which are not necessarily shared by manual aiming.

Targeting Therapy Resistance: When Glutamine Catabolism Becomes Essential.

PubMed

Lukey, Michael J; Katt, William P; Cerione, Richard A

2018-05-14

Identifying contexts in which cancer cells become addicted to specific nutrients is critical for developing targeted metabolic therapies. In this issue of Cancer Cell, Momcilovic et al. report that suppressed glycolysis following mTOR inhibition is countered by adaptive glutamine catabolism in lung squamous cell carcinoma, sensitizing tumors to glutaminase inhibition. Copyright © 2018 Elsevier Inc. All rights reserved.

Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy.

PubMed

Nogueira-Librelotto, Daniele R; Codevilla, Cristiane F; Farooqi, Ammad; Rolim, Clarice M B

2017-01-01

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Single-session manualized ego state therapy (EST) for combat stress injury, PTSD, and ASD, part 1: the theory.

PubMed

Barabasz, Arreed F; Barabasz, Marianne; Watkins, John G

2011-01-01

Ego state therapy (EST) evolved from a psychodynamic understanding of personality as a product of an individual's ego states to a conceptualization of how ego-energized and object-energized elements are bound together to cope with a traumatic event. Neurobiological studies now substantiate Watkins's war neuroses conceptualizations. Because of their severity, trauma memories are encoded in the subcortical-subconscious brain regions that are accessed by the single-session manualized EST procedure but not by the popular cognitive-behavioral management therapies. The imprint of the trauma is not accessible or resolvable by such top-down verbal understanding or reframing; EST is a bottom-up therapy. Abreactive hypnosis facilitates ego state expression at physiologically and psychologically intense levels sufficient to activate subcortical processes to release affect in the presence of the therapist, who adds ego strength to the patient. This is followed by interpretation and reintegration. The result is a reconstructed personality that is adaptive and resilient.

The Mechanisms of Manual Therapy in the Treatment of Musculoskeletal Pain: A Comprehensive Model

PubMed Central

Bialosky, Joel E; Bishop, Mark D; Price, Don D; Robinson, Michael E; George, Steven Z

2009-01-01

Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms. PMID:19027342

Targeting the Epigenome in Lung Cancer: Expanding Approaches to Epigenetic Therapy

PubMed Central

Jakopovic, Marko; Thomas, Anish; Balasubramaniam, Sanjeeve; Schrump, David; Giaccone, Giuseppe; Bates, Susan E.

2013-01-01

Epigenetic aberrations offer dynamic and reversible targets for cancer therapy; increasingly, alteration via overexpression, mutation, or rearrangement is found in genes that control the epigenome. Such alterations suggest a fundamental role in carcinogenesis. Here, we consider three epigenetic mechanisms: DNA methylation, histone tail modification and non-coding, microRNA regulation. Evidence for each of these in lung cancer origin or progression has been gathered, along with evidence that epigenetic alterations might be useful in early detection. DNA hypermethylation of tumor suppressor promoters has been observed, along with global hypomethylation and hypoacetylation, suggesting an important role for tumor suppressor gene silencing. These features have been linked as prognostic markers with poor outcome in lung cancer. Several lines of evidence have also suggested a role for miRNA in carcinogenesis and in outcome. Cigarette smoke downregulates miR-487b, which targets both RAS and MYC; RAS is also a target of miR-let-7, again downregulated in lung cancer. Together the evidence implicates epigenetic aberration in lung cancer and suggests that targeting these aberrations should be carefully explored. To date, DNA methyltransferase and histone deacetylase inhibitors have had minimal clinical activity. Explanations include the possibility that the agents are not sufficiently potent to invoke epigenetic reversion to a more normal state; that insufficient time elapses in most clinical trials to observe true epigenetic reversion; and that doses often used may provoke off-target effects such as DNA damage that prevent epigenetic reversion. Combinations of epigenetic therapies may address those problems. When epigenetic agents are used in combination with chemotherapy or targeted therapy it is hoped that downstream biological effects will provoke synergistic cytotoxicity. This review evaluates the challenges of exploiting the epigenome in the treatment of lung cancer

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

PubMed Central

Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

2017-01-01

Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

Driver genes in non-small cell lung cancer: Characteristics, detection methods, and targeted therapies

PubMed Central

He, Bing; Zhang, Hu-Qin

2017-01-01

Lung cancer is one of the most common causes of cancer-related death in the world. The large number of lung cancer cases is non-small cell lung cancer (NSCLC), which approximately accounting for 75% of lung cancer. Over the past years, our comprehensive knowledge about the molecular biology of NSCLC has been rapidly enriching, which has promoted the discovery of driver genes in NSCLC and directed FDA-approved targeted therapies. Of course, the targeted therapies based on driver genes provide a more exact option for advanced non-small cell lung cancer, improving the survival rate of patients. Now, we will review the landscape of driver genes in NSCLC including the characteristics, detection methods, the application of target therapy and challenges. PMID:28915704

Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

PubMed

Chen, Branson; Lee, Jong Bok; Kang, Hyeonjeong; Minden, Mark D; Zhang, Li

2018-04-24

While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as

Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress

PubMed Central

Garg, Abhishek D; Maes, Hannelore; van Vliet, Alexander R; Agostinis, Patrizia

2015-01-01

The endoplasmic reticulum (ER) is at the center of a number of vital cellular processes such as cell growth, death, and differentiation, crosstalk with immune or stromal cells, and maintenance of proteostasis or homeostasis, and ER functions have implications for various pathologies including cancer. Recently, a number of major hallmarks of cancer have been delineated that are expected to facilitate the development of anticancer therapies. However, therapeutic induction of ER stress as a strategy to broadly target multiple hallmarks of cancer has been seldom discussed despite the fact that several primary or secondary ER stress-inducing therapies have been found to exhibit positive clinical activity in cancer patients. In the present review we provide a brief historical overview of the major discoveries and milestones in the field of ER stress biology with important implications for anticancer therapy. Furthermore, we comprehensively discuss possible strategies enabling the targeting of multiple hallmarks of cancer with therapy-induced ER stress. PMID:27308392

Manual therapy, exercise therapy or combined treatment in the management of adult neck pain - A systematic review and meta-analysis.

PubMed

Fredin, Ken; Lorås, Håvard

2017-10-01

Neck pain is a common and often disabling musculoskeletal condition. Two therapies frequently prescribed for its management are manual therapy (MT) and exercise therapy (ET), and combining these treatment approaches are common. To assess whether or not combined treatment consisting of MT and ET is more effective than either therapy alone in relieving pain and improving function in adult patients with grade I-II neck pain. Systematic review with meta-analysis. A systematic search on EMBASE, MEDLINE, AMED, CENTRAL and PEDro were performed until June 2017. Randomized controlled trials with adult grade I-II neck pain patients were included if they investigated the combined effect of MT and ET to the same ET or MT alone, and reported pain intensity or disability on numerical scales. Quality of life was assessed as a secondary outcome. Quality of the included trials was assessed with the PEDro scale, and the quality of evidence was assessed with GRADE. 1169 articles were screened, and 7 studies were included, all of which investigated the addition of ET to MT. Only very small and non-significant between group differences was found on pain intensity at rest, neck disability, and quality of life at immediate post-treatment, 6 months, and 12 months follow-up. The quality of evidence was moderate for pain-at-rest outcomes and moderate too low for neck disability and quality of life outcomes. Combined treatment consisting of MT and ET does not seem to be more effective in reducing neck pain intensity at rest, neck disability or improving quality of life in adult patients with grade I-II neck pain, than ET alone. Copyright © 2017 Elsevier Ltd. All rights reserved.