BackgroundThere are inconsistencies in the literature regarding the prevalence and assessment of chemotherapy-induced peripheral neuropathy (CIPN). This study explored CIPN natural history and its characteristics in patients receiving taxane- and platinum-based chemotherapy.Patients and methodsMulti-country multisite prospective longitudinal observational study. Patients were assessed before commencing and three weekly during chemotherapy for up to six cycles, and at 6,9, and 12 months using clinician-based scales (NCI-CTCAE; WHO-CIPN criterion), objective assessments (cotton wool test;10 g monofilament); patient-reported outcome measures (FACT/GOG-Ntx; EORTC-CIPN20), and Nerve Conduction Studies.ResultsIn total, 343 patients were recruited in the cohort, providing 2399 observations. There was wide variation in CIPN prevalence rates using different assessments (14.2–53.4%). Prevalence of sensory neuropathy (and associated symptom profile) was also different in each type of chemotherapy, with paclitaxel (up to 63%) and oxaliplatin (up to 71.4%) showing the highest CIPN rates in most assessments and a more complex symptom profile. Peak prevalence was around the 6-month assessment (up to 71.4%). Motor neurotoxicity was common, particularly in the docetaxel subgroup (up to 22.1%; detected by NCI-CTCAE). There were relatively moderately-to-low correlations between scales (rs = 0.15,p < 0.05-rs = 0.48 p < 0.001), suggesting that they measure different neurotoxicity aspects from each other. Cumulative chemotherapy dose was not associated with onset and course of CIPN.ConclusionThe historical variation reported in CIPN incidence and prevalence is possibly confounded by disagreement between assessment modalities. Clinical practice should consider assessment of motor neuropathy for neurotoxic chemotherapy. Current scales may not be all appropriate to measure CIPN in a valid way, and a combination of scales are needed.

BackgroundPeripheral neuropathy (PN) due to paclitaxel is a common dose-limiting toxicity with no effective prevention or treatment. We hypothesize that continuous-flow limb hypothermia can reduce paclitaxel-induced PN.Patients and methodsAn internally controlled pilot trial was conducted to investigate the neuroprotective effect of continuous-flow limb hypothermia in breast cancer patients receiving weekly paclitaxel. Patients underwent limb hypothermia of one limb for a duration of 3 h with every paclitaxel infusion, with the contralateral limb used as control. PN was primarily assessed using nerve conduction studies (NCSs) before the start of chemotherapy, and after 1, 3, and 6 months. Skin temperature and tolerability to hypothermia were monitored using validated scores.ResultsTwenty patients underwent a total of 218 cycles of continuous-flow limb hypothermia at a coolant temperature of 22°C. Continuous-flow limb hypothermia achieved mean skin temperature reduction of 1.5 ± 0.7°C and was well tolerated, with no premature termination of cooling due to intolerance. Grade 3 PN occurred in 2 patients (10%), grade 2 in 2 (10%), and grade 1 in 12 (60%). Significant correlation was observed between amount of skin cooling and motor nerve amplitude preservation at 6 months (p < 0.0005). Sensory velocity and amplitude in the cooled limbs were less preserved than in the control limbs, but the difference did not attain statistical significance. One patient with a history of diabetes mellitus had significant preservation of compound muscle action potential in the cooled limb on NCS analysis.ConclusionThis study suggests that continuous limb hypothermia accompanying paclitaxel infusion may reduce paclitaxel-induced PN and have therapeutic potential in select patients and warrants further investigation. The method is safe and well tolerated.

Dual-targeted organic nanoparticles efficiently target the margin of glioblastoma and successfully suppress the tumour growth through photothermal therapy.

present safety challenges. Evans blue (EB) assay remains the most commonly used method for the evaluation of BBB damage in the experimental studies of brain injury. [ 7 ] The EB dye works, as widely claimed, based on its ability to bind to serum albumin immediately following its intravenous injection. [ 8,9 ] Although this assay is widely used in numerous studies, EB dye has several limitations as a biomarker, such as its lethal toxicity in vivo and confounding problems in quantitative assessments via various spectroscopic methods. [10][11][12] Therefore, a sensitive, selective, and nontoxic method for evaluating BBB damage and vascular leakage is highly desirable.Fluorogens with aggregation-induced emission characteristics (AIEgens) have been developed for various biological applications in recent years. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] Compared to traditional fl uorogens, which suffer from aggregation-caused quenching phenomenon at high concentrations, AIEgens show very weak fl uorescence in molecularly dissolved state but bright emission in aggregate state due to the inhibition of energy dissipation and restriction of intramolecular motion. [ 13,15,27,28 ] This unique property makes AIEgens great candidates for the design of light-up probes [29][30][31][32][33] and ultrabright organic nanoparticles (NPs) [ 26,27,34,35 ] for sensing and imaging applications. Recently, our group and others have reported several AIEgen NPs for cell tracing [36][37][38] and vascular imaging [ 34,39 ] with high brightness, good contrast, and nonobservable leakage, which provide the opportunity to further explore their potentials for practical biological problems, such as the evaluation of BBB damage and the resulted vascular leakage.To develop a sensitive and selective optical imaging method based on AIEgen NPs that can precisely test BBB integrity and map vascular leakage in animal models, in this work, we utilized 2,3-bis(4-(phenyl(4-(1,2,2-triphenylvinyl)phenyl)amino)phenyl)fumaronitrile (TPETPAFN), an AIEgen with bright red emission in the solid state and developed a strategy to fabricate NPs with controlled sizes of 60, 30, and 10 nm. [ 40 ] The good photostability and biocompatibility of these NPs guarantee the in vivo investigation of BBB. A rat model of photothrombotic ischemia (PTI) was selected to induce the BBB damage. Compared to the widely used ischemia models (middle cerebral artery occlusion), our model could produce ischemic stroke at a targeted single blood vessel with precise location, controlled size, and well-delimited boundary, which could ensure the precise evaluation of BBB integrity. [ 41,42 ] Using this model, we evaluated the integrity of the BBB during the hyperacute phase of ischemia using the TPETPAFN NPs. The extent of NP leakage in various brain locations in response to BBB disruption post The blood-brain barrier (BBB) is a specialized cerebral vascular system which is responsible for strict regulation of paracellular permeability and mediates entry of blood-borne substances in...

Noninvasive and nonionizing imaging of sentinel lymph nodes (SLN) is highly desirable for the detection of breast cancer metastasis through sentinel lymph node biopsy. Photoacoustic (PA) imaging is an emerging imaging technique that can serve as a suitable approach for SLN imaging. Herein, novel conjugated oligomer based nanoparticles (NPs) with strong NIR absorption, good biocompatibility, excellent PA contrast, and good photothermal conversion efficiency are reported. Real-time PA imaging of SLN reveals high resolution of the NPs via injection from the left forepaw pad. In addition, the surface functionalized NPs can target breast cancer cells and kill them efficiently and specifically through photothermal therapy upon 808 nm laser irradiation. This work shows great potential of the nanoparticle PA contrast agent to serve as a multifunctional probe for photothermal therapy at SLNs to achieve the inhibition of cancer cell metastasis in the near future.

Infrared-emitting rare-earth (ytterbium and erbium) doped nanoparticles (REDNPs) have recently emerged as an excellent probe for both deep tissue luminescence and photoacoustic (PA) imaging with high resolutions and contrast. Here we report on the first study of the size and surface effects of the infrared PA imaging of dual modal REDNPs. We show that the PA signal amplitude generated by REDNPs is increased by increasing the size and coating the inorganic shell (undoped NaYF4 or silica). We have also discovered that the choice of the coating material is critical as undoped NaYF4 shell was able to enhance PA signal amplitude (by up to ∼30%) and infrared emission (19 times) simultaneously. The simultaneous enhancement of PA signal amplitude and infrared emission was due to increased phonon modes and reduced surface effects. The in vivo PA images obtained demonstrated that in addition to being excellent luminescent probes, the REDNPs also performed as successful PA contrast agents to visualize rodent cortical blood vessels.

No abstract

Purpose Severe peripheral neuropathy is a common dose-limiting toxicity of taxane chemotherapy, with no effective treatment. Frozen gloves have shown to reduce the severity of neuropathy in several studies but comes with the incidence of undesired side effects such as cold intolerance and frostbite in extreme cases. A device with thermoregulatory features which can safely deliver tolerable amounts of cooling while ensuring efficacy is required to overcome the deficiencies of frozen gloves. The role of continuous-flow cooling in prevention of neurotoxicity caused by paclitaxel has been previously described. This study hypothesized that cryocompression (addition of dynamic pressure to cooling) may allow for delivery of lower temperatures with similar tolerance and potentially improve efficacy. Method A proof-of-concept study was conducted in cancer patients receiving taxane chemotherapy. Each subject underwent four-limb cryocompression with each chemotherapy infusion (three hours) for a maximum of 12 cycles. Cryocompression was administered at 16°C and cyclic pressure (5-15 mmHg). Skin surface temperature and tolerance scores were recorded. Neuropathy was assessed using clinician-graded peripheral sensory neuropathy scores, total neuropathy score (TNS) and nerve conduction studies (NCS) conducted before (NCS pre), after completion (NCS post) and 3 months post-chemotherapy (NCS 3m). Results were retrospectively compared with patients who underwent paclitaxel chemotherapy along with continuous-flow cooling and controls with no hypothermia. Results In total, 13 patients underwent 142 cycles of cryocompression concomitant with chemotherapy. Limb hypothermia was well tolerated, and only 1 out of 13 patients required an intra-cycle temperature increase, with no early termination of cryocompression in any subject. Mean skin temperature reduction of 3.8 ± 1.7°C was achieved. Cryocompression demonstrated significantly greater skin temperature reductions compared to continuous-flow cooling and control (p < 0.0001). None of the patients experienced severe neuropathy (clinician-assessed neuropathy scores of grade 2 or higher). NCS analysis showed preservation of motor amplitudes at NCS 3m in subjects who underwent cryocompression, compared to the controls who showed Electronic supplementary material The online version of this article (