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The Lancet. Oncology Jun 2024Theranostics has become a major area of innovation and progress in cancer care over the last decade. In view of the introduction of approved therapeutics in... (Review)
Review
Theranostics has become a major area of innovation and progress in cancer care over the last decade. In view of the introduction of approved therapeutics in neuroendocrine tumours and prostate cancer in the last 10 years, the ability to provide access to these treatments has emerged as a key factor in ensuring global benefits from this cancer therapy approach. In this Series paper we explore the issues that affect access to and availability of theranostic radiopharmaceuticals, including supply and regulatory issues that might affect the availability of theranostic treatments for patients with cancer.
Topics: Humans; Radiopharmaceuticals; Theranostic Nanomedicine; Neoplasms; Precision Medicine
PubMed: 38821100
DOI: 10.1016/S1470-2045(24)00041-X -
Journal of Nuclear Medicine : Official... Feb 2024Therapeutic approaches to brain tumors remain a challenge, with considerable limitations regarding delivery of drugs. There has been renewed and increasing interest in...
Therapeutic approaches to brain tumors remain a challenge, with considerable limitations regarding delivery of drugs. There has been renewed and increasing interest in translating the popular theranostic approach well known from prostate and neuroendocrine cancer to neurooncology. Although far from perfect, some of these approaches show encouraging preliminary results, such as for meningioma and leptomeningeal spread of certain pediatric brain tumors. In brain metastases and gliomas, clinical results have failed to impress. Perspectives on these theranostic approaches regarding meningiomas, brain metastases, gliomas, and common pediatric brain tumors will be discussed. For each tumor entity, the general context, an overview of the literature, and future perspectives will be provided. Ongoing studies will be discussed in the supplemental materials. As most theranostic agents are unlikely to cross the blood-brain barrier, the delivery of these agents will be dependent on the successful development and clinical implementation of techniques enhancing permeability and retention. Moreover, the international community should strive toward sufficiently large and randomized studies to generate high-level evidence on theranostic approaches with radioligand therapies for central nervous system tumors.
Topics: Male; Child; Humans; Precision Medicine; Theranostic Nanomedicine; Brain Neoplasms; Blood-Brain Barrier; Glioma
PubMed: 38071569
DOI: 10.2967/jnumed.123.266205 -
Small (Weinheim An Der Bergstrasse,... Oct 2023The rapid development of nanomedicine and nanobiotechnology has allowed the emergence of various therapeutic modalities with excellent therapeutic efficiency and... (Review)
Review
The rapid development of nanomedicine and nanobiotechnology has allowed the emergence of various therapeutic modalities with excellent therapeutic efficiency and biosafety, among which, the sonodynamic therapy (SDT), a combination of low-intensity ultrasound and sonosensitizers, is emerging as a promising noninvasive treatment modality for cancer treatment due to its deeper penetration, good patient compliance, and minimal damage to normal tissue. The sonosensitizers are indispensable components in the SDT process because their structure and physicochemical properties are decisive for therapeutic efficacy. Compared to the conventional and mostly studied organic sonosensitizers, inorganic sonosensitizers (noble metal-based, transition metal-based, carbon-based, and silicon-based sonosensitizers) display excellent stability, controllable morphology, and multifunctionality, which greatly expand their application in SDT. In this review, the possible mechanisms of SDT including the cavitation effect and reactive oxygen species generation are briefly discussed. Then, the recent advances in inorganic sonosensitizers are systematically summarized and their formulations and antitumor effects, particularly highlighting the strategies for optimizing the therapeutic efficiency, are outlined. The challenges and future perspectives for developing state-of-the-art sonosensitizers are also discussed. It is expected that this review will shed some light on future screening of decent inorganic sonosensitizers for SDT.
Topics: Humans; Neoplasms; Ultrasonic Therapy; Combined Modality Therapy; Theranostic Nanomedicine; Nanomedicine; Reactive Oxygen Species
PubMed: 37323087
DOI: 10.1002/smll.202303195 -
Cannabis and Cannabinoid Research Aug 2023This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for... (Review)
Review
This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Eleven more studies were found in clinical trial databases but not accessible. Symptoms targeted were dermatopathologies or safety (two studies), pain (two), and behavior (one). Doses were 50-250 mg or 0.075-1.0% CBD, but coformulated with other ingredients. Risk of bias was high and reporting deficiencies further compromised data reliability. Diverse methodologies and formulations hampered syntheses for CBD dose, efficacy, and safety. Plasma CBD levels in dogs and rodents were 0.01-5 μM translating to <100 nM free, unbound CBD in humans. Adverse events were uncommon and mild, but meaningless without CBD's contribution to efficacy data. Achievable CBD plasma concentrations ∼100 nM can interact predominantly with high-affinity CBD targets, for example, TRPA1 and TRPM8 membrane channels that are abundantly expressed in pathological conditions. Even if reached, higher CBD concentrations on less susceptible targets risk complex and unsafe CBD therapy. A conceptual framework is proposed where dermal capillary loops create sinking for topical CBD demonstrating parallels between topical and transdermal CBD administration. Users risk generalizing inadequately designed trials to all CBD preparations. New clinical trials are urgently needed: they must demonstrate that outcomes are solely from CBD pharmacology, are reliable, unbiased, safe, and comparable. Measurements of sustained plasma CBD levels are mandatory, irrespective of administration route for successful translation from systems that express human molecular targets. Placebos must be appropriate. Transcutaneous and topical formulations need preliminary studies to optimize CBD skin penetration. Then, users can rationally balance efficacy against potential harms and cost-effectiveness of CBD formulations.
Topics: Humans; Animals; Dogs; Cannabidiol; Reproducibility of Results; Pain; Administration, Cutaneous; Seizures
PubMed: 35605018
DOI: 10.1089/can.2021.0154 -
Angewandte Chemie (International Ed. in... Aug 2023Photoresponsive materials offer excellent spatiotemporal control over biological processes and the emerging phototherapeutic methods are expected to have significant... (Review)
Review
Photoresponsive materials offer excellent spatiotemporal control over biological processes and the emerging phototherapeutic methods are expected to have significant effects on targeted cancer therapies. Recent examples show that combination of photoactivatable approaches with bioorthogonal chemistry enhances the precision of targeted phototherapies and profound implications are foreseen particularly in the treatment of disperse/diffuse tumors. The extra level of on-target selectivity and improved spatial/temporal control considerably intensified related bioorthogonally assisted phototherapy research. The anticipated growth of further developments in the field justifies the timeliness of a brief summary of the state of the art.
Topics: Humans; Phototherapy; Neoplasms; Theranostic Nanomedicine
PubMed: 37161824
DOI: 10.1002/anie.202303198 -
Neuromodulation : Journal of the... Dec 2023The magnitude of the placebo response depends on both the modality used as the "placebo" and the intervention with which it is compared, both of which can complicate the...
BACKGROUND
The magnitude of the placebo response depends on both the modality used as the "placebo" and the intervention with which it is compared, both of which can complicate the interpretation of randomized controlled trials (RCTs) for depression in late life. Given that neurostimulation and pharmacotherapy are among the most common interventions studied for late-life depression, comparing the relative placebo responses in studies of these interventions can aid interpretation of relative effect sizes.
MATERIALS AND METHODS
We analyzed data from two RCTs of adults aged ≥60 years in an episode of treatment-resistant major depression, one comparing aripiprazole and matching placebo pills and the other comparing deep repetitive transcranial magnetic stimulation (rTMS) and sham rTMS. In both RCTs, depression was assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary comparison occurred after four weeks using analysis of covariance (ANCOVA) of HDRS-17 scores in participants who received placebo pills or sham rTMS. Relevant covariates included years of education, duration of depressive episode, and baseline HDRS-17 score.
RESULTS
Accounting for covariates, there was a larger reduction of HDRS-17 after four weeks in the sham rTMS group (estimated marginal mean ± SE: -5.90 ± 1.45; 95% CI: [-8.82, 2.98]) than in the placebo pills group (-1.07 ± 1.45; [-3.98, 1.85]). There were no significant differences between these groups in the binary outcome analysis of response and remission rates at four weeks or any outcome at trial end point comparison.
CONCLUSIONS
Sham rTMS may have a larger placebo response than placebo pills early in the treatment of older adults with treatment-resistant depression. Differential placebo responses should be considered in both the interpretation and design of RCTs.
Topics: Humans; Aged; Depression; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Placebo Effect; Treatment Outcome; Double-Blind Method
PubMed: 35088720
DOI: 10.1016/j.neurom.2021.10.019 -
Pain Nov 2023Observing someone experience pain relief or exacerbation after an intervention may induce placebo hypoalgesia or nocebo hyperalgesia. Understanding the factors that... (Meta-Analysis)
Meta-Analysis
Observing someone experience pain relief or exacerbation after an intervention may induce placebo hypoalgesia or nocebo hyperalgesia. Understanding the factors that contribute to these effects could help in the development of strategies for optimizing treatment of chronic pain conditions. We systematically reviewed and meta-analyzed the literature on placebo hypoalgesia and nocebo hyperalgesia induced by observational learning (OL). A systematic literature search was conducted in the databases PubMed, PsycINFO, Web of Science, ScienceDirect, PsycARTICLES, Scopus, and Academic Search Ultimate. Twenty-one studies were included in the systematic review, 17 of which were suitable for meta-analysis (18 experiments; n = 764 healthy individuals). The primary end point was the standardized mean difference (SMD) for pain following placebo cues associated during OL with low vs high pain. Observational learning had a small-to-medium effect on pain ratings (SMD 0.44; 95% confidence interval [CI] 0.21-0.68; P < 0.01) and a large effect on pain expectancy (SMD 1.11; 95% CI 0.49-2.04; P < 0.01). The type of observation (in-person vs videotaped) modulated the magnitude of placebo hypoalgesia/nocebo hyperalgesia ( P < 0.01), whereas placebo type did not ( P = 0.23). Finally, OL was more effective when observers' empathic concern (but no other empathy-related factors) was higher ( r = 0.14; 95% CI 0.01-0.27; P = 0.03). Overall, the meta-analysis demonstrates that OL can shape placebo hypoalgesia and nocebo hyperalgesia. More research is needed to identify predictors of these effects and to study them in clinical populations. In the future, OL could be an important tool to help maximize placebo hypoalgesia in clinical settings.
Topics: Humans; Hyperalgesia; Nocebo Effect; Pain; Learning; Pain Perception; Placebo Effect
PubMed: 37326688
DOI: 10.1097/j.pain.0000000000002943 -
Advances in Colloid and Interface... Aug 2024To overcome the challenges of poor wound diagnosis and limited clinical efficacy of current wound management, wound dressing materials with the aim of monitoring various... (Review)
Review
To overcome the challenges of poor wound diagnosis and limited clinical efficacy of current wound management, wound dressing materials with the aim of monitoring various biomarkers vital to the wound healing process such as temperature, pH, glucose concentration, and reactive oxygen species (ROS) and improving the therapeutic outcomes have been developed. These innovative theranostic dressings are smartly engineered using stimuli-responsive biomaterials to monitor and regulate local microenvironments and deliver cargos to the wound sites in a timely and effective manner. This review provides an overview of recent advances in novel theranostics for wound monitoring and therapy as well as giving insights into the future treatment of wounds via smart design of theranostic materials.
Topics: Humans; Wound Healing; Theranostic Nanomedicine; Bandages; Hydrogen-Ion Concentration; Animals; Reactive Oxygen Species; Biocompatible Materials
PubMed: 38843699
DOI: 10.1016/j.cis.2024.103207 -
European Heart Journal. Quality of Care... Aug 2023Randomized controlled trials (RCTs) of lipid-lowering therapy (LLT) in which the control groups received placebo without background LLT offer unique insights into the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Randomized controlled trials (RCTs) of lipid-lowering therapy (LLT) in which the control groups received placebo without background LLT offer unique insights into the placebo and nocebo effects of lipid-lowering RCTs.
METHODS AND RESULTS
Embase and Medline were searched for hyperlipidaemia RCTs with placebo-controlled arms. Placebo arms with background LLT were excluded. A single arm meta-analysis of proportions was used to estimate major adverse cardiovascular events (MACE) and adverse events (AE). A meta-analysis of means was used to estimate the pooled mean differences of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoproteins (HDL) and triglycerides (TG).A total of 40 RCTs and 37 668 placebo-treated participants were included. The pooled mean changes for TC, LDL, HDL, and TG were -0.019 mmol/L, -0.028 mmol/L, 0.013 mmol/L, and 0.062 mmol/L respectively among placebo-treated participants, indicating a modest placebo effect. The pooled average nocebo effect among placebo-treated participants was 42.62% for all AEs and 3.38% for musculoskeletal-related AEs, 11.36% for gastrointestinal-related AEs, and 6.62% for headaches. Placebo-treated participants in secondary prevention RCTs had a far higher incidence of these nocebo effects than primary prevention RCTs: any AEs (OR 6.76, 95% CI: 5.56-8.24, P < 0.001), and gastrointestinal-related AE (OR 1.23, 95% CI: 1.00-1.51, P = 0.049). No differences in nocebo effects were found between the placebo arms of statin and non-statin trials.
CONCLUSION
Our meta-analysis of placebo-treated participants in RCTs with no background LLT indicate a modest placebo effect but prominent nocebo effect of musculoskeletal, headache, and gastrointestinal symptoms that was greatest among secondary prevention RCTs. These findings may inform the design of future LLT RCTs.
Topics: Humans; Nocebo Effect; Randomized Controlled Trials as Topic; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids
PubMed: 36107462
DOI: 10.1093/ehjqcco/qcac060 -
Advanced Healthcare Materials Jun 2024Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular... (Review)
Review
Atherosclerotic plaque formation is considered the primary pathological mechanism underlying atherosclerotic cardiovascular diseases, leading to severe cardiovascular events such as stroke, acute coronary syndromes, and even sudden cardiac death. Early detection and timely intervention of plaques are challenging due to the lack of typical symptoms in the initial stages. Therefore, precise early detection and intervention play a crucial role in risk stratification of atherosclerotic plaques and achieving favorable post-interventional outcomes. The continuously advancing nanoplatforms have demonstrated numerous advantages including high signal-to-noise ratio, enhanced bioavailability, and specific targeting capabilities for imaging agents and therapeutic drugs, enabling effective visualization and management of atherosclerotic plaques. Motivated by these superior properties, various noninvasive imaging modalities for early recognition of plaques in the preliminary stage of atherosclerosis are comprehensively summarized. Additionally, several therapeutic strategies are proposed to enhance the efficacy of treating atherosclerotic plaques. Finally, existing challenges and promising prospects for accelerating clinical translation of nanoplatform-based molecular imaging and therapy for atherosclerotic plaques are discussed. In conclusion, this review provides an insightful perspective on the diagnosis and therapy of atherosclerotic plaques.
Topics: Humans; Plaque, Atherosclerotic; Animals; Theranostic Nanomedicine; Nanoparticles
PubMed: 38564883
DOI: 10.1002/adhm.202303612