Contrast-enhanced ultrasound of polyp malignant transformation with multiple metastases in a patient with Peutz-Jeghers syndrome.

Multi-systemic metastasis in patients with Peutz-Jeghers syndrome (PJS) is very rare, and there are nearly no relevant imaging reports, especially in contrast-enhanced ultrasound (CEUS). We present here a 40-year-old male patient who underwent several partial small bowel resections and endoscopic polypectomy for intestinal polyps. After reviewing the patient's clinical diagnosis and treatment process, CEUS with sulfur hexafluoride microbubbles (SonoVue, Bracco, Milan, Italy) in the liver and gastrointestinal tract was performed. We imaged multiple abnormal masses with sonographic features consistent with malignancies. Combined with other imaging examinations and 18 gauge core-needle puncture biopsy of liver masses, multiple metastases outside the gastrointestinal tract were considered. This case report suggests CEUS may be an easy, effective, and supplementary method for evaluating PJS patients with suspected multi-systemic malignant lesions including the gastrointestinal tract.

Age-related trends in the incidence of metastatic colorectal cancer from 2010 to 2019 in the USA.

Aim: To evaluate temporal changes in metastatic colorectal cancer (mCRC), incidence, and use of chemotherapy treatment by age group using real-world data (RWD) from the USA. Methods: A retrospective, observational study describing temporal trends in mCRC incidence and FOLFOXIRI treatment by age group using a nationwide database of commercially and Medicare Advantage-insured patients from 2010 to 2019. Results: Incidence of mCRC increased by 22.1 and 14.9% in the 18-49 and 50-64 years cohorts, respectively, and decreased by 21.6% in the ≥65 years cohort. Overall, younger patients were more likely to receive FOLFOXIRI treatment versus older patients. Conclusion: The shifting age distribution of mCRC should be considered when recommending screening and treatment. Further research is needed to inform age-specific treatment guidelines.

What is this article about? This article reports the results of a study that used a US database of commercially and Medicare Advantage-insured adults to evaluate how the number of adults with metastatic colorectal cancer (mCRC) in three age groups (18­49 years, 50­64 years and 65 years and over) changed from 2010 to 2019. The study also looked at the use of an aggressive chemotherapy treatment, known as 5-fluorouracil, oxaliplatin, leucovorin calcium and irinotecan (FOLFOXIRI), by age group. What were the results? Overall, 23,970 adults with mCRC were included in the study. From 2010 to 2019, the number of adults with mCRC increased by 22.1% among those aged 18­49 years, increased by 14.9% among those aged 50­64 years, and decreased by 21.6% among those aged 65 years and over. There were some differences between age groups; a higher percentage of younger patients (18­49 years) were Hispanic or Asian, and from the South compared with the older age groups. In comparison, those aged 65 years and over were more likely to be from the West and Northeast of the USA. The study also found that a higher proportion of those aged 18­49 years received FOLFOXIRI (8.4%) compared with adults aged 50­64 years (4.4%) and 65 years and over (1.9%). What do the results of the study mean? Healthcare providers should be aware that early-onset mCRC is becoming more common and consider this when recommending screening and treatment.

Comparative risk of dementia among patients with atrial fibrillation treated with catheter ablation versus anti-arrhythmic drugs.

Atrial fibrillation (AF) is associated with an increased risk of dementia. Emerging evidence suggests AF suppression is associated with reduced risk of dementia, but the optimal strategy to achieve this is unknown. We sought to compare the risk of dementia in patients with AF who underwent catheter ablation (CA) versus anti-arrhythmic drug (AAD) treatment. METHODS AND RESULTS: Using the 2000 to 2021 Optum Clinformatics database, patients with AF who underwent CA versus AAD treatment (≥1 prescription fill for ≥2 different AADs) were identified and propensity score matched overall and within sex subgroups. A cause-specific hazard model was performed to assess dementia overall and in sex-specific subgroups. After matching, there were 19,088 patients per group. CA was associated with a 41% lower risk of dementia compared with AAD alone (1.9% vs 3.3%; hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.52-0.67, log-rank P < .0001). When examined by sex, dementia risk reduction associated with CA versus AAD use alone was observed among both males (HR 0.55, 95% CI 0.46-0.66) and females (HR 0.60, 95% CI 0.50-0.72). Though not studied as a primary outcome, patients treated with CA were also observed to have 49% lower associated risk of mortality compared with AAD only (HR 0.51 95% CI 0.46-0.55, P < .0001). CONCLUSIONS: Among patients treated for AF, CA was associated with significantly lower risk of dementia and death compared with AADs only. These reductions in risk associated with CA versus AAD were seen in both males and females.

Same-day discharge after catheter ablation in patients with atrial fibrillation in a large nationwide administrative claims database.

BACKGROUND: Catheter ablation (CA) is a common treatment for atrial fibrillation (AF). This study evaluated outcomes of same day discharge (SDD) versus overnight stay (ONS) among AF patients undergoing outpatient CA. METHODS: The Optum SES Clinformatics Extended Data Mart database was used to identify patients ≥18 years of age undergoing outpatient CA for AF (2016-2020). Eligible patients were indexed to the date of first CA and classified into SDD and ONS groups based on the length of service. A 1:3 propensity score matching was used to create comparable SDD:ONS samples. The primary safety outcome was CA-related complications within 30 days of index procedure. The primary efficacy outcome was AF recurrence within 1 year. Cox proportional hazards models were estimated for outcome comparison. RESULTS: In the postmatch 30-day cohort for safety evaluation, there were 6600 patients (1660 [25.2%] SDD; 4940 [74.8%] ONS), with a mean age of 66.6 years. There was no significant difference in the 30-day composite rate of postablation complications (4.7% [78/1660] vs. 3.8% [187/4940]; p = 0.100) and 1-year composite rate of AF recurrence (14.3% [142/996] vs. 14.5% [430/2972]; p = 0.705) between the SDD and ONS groups. CONCLUSION: This study demonstrated that SDD following CA to treat patients with AF is safe, with low rates of postablation complications and AF recurrence, which were comparable to rates in patients with an ONS after CA.

Research of Fluorescent Properties of a New Type of Phosphor with Mn2+-Doped Ca2SiO4.

Fluorescent optical fiber temperature sensors have attracted extensive attention due to their strong anti-electromagnetic interference ability, good high-voltage insulation performance, and fast response speed. The fluorescent material of the sensor probe directly determines the temperature measurement effect. In this paper, a new type of fluorescent material with a Mn2+-doped Ca2SiO4 phosphor (CSO:Mn2+) is synthesized via the solid-state reaction method at 1450 °C. The X-ray diffraction spectrum shows that the sintered sample has a pure phase structure, although the diffraction peaks show a slight shift when dopants are added. The temperature dependence of the fluorescence intensity and lifetime in the range from 290 to 450 K is explored with the help of a fluorescence spectrometer. Green emission bands peaking at 475 and 550 nm from Mn2+ are observed in the fluorescence spectra, and the intensity of emitted light decreases as the temperature rises. The average lifetime of CSO:Mn2+ is 17 ms, which is much higher than the commonly used fluorescent materials on the market. The fluorescence lifetime decreases with increasing temperature and shows a good linear relationship within a certain temperature range. The research results are of great significance to the development of a new generation of fluorescence sensors.

Global Temperature Sensing for an Operating Power Transformer Based on Raman Scattering.

Traditional monitoring methods cannot obtain the overall thermal information for power transformers. To solve this problem, a distributed fiber optic sensor (DFOS) was creatively applied inside an operating 35 kV power transformer by highly integrating with the electromagnetic wires. Then, the transformer prototype with totally global sensing capability was successfully developed and it was qualified for power grid application through the strict ex-factory tests. The as designed optical fiber sensor works stably all the time with a temperature accuracy of ±0.2 °C and spatial positioning accuracy of 0.8 m. Based on the obtained internal temperature distribution, Gaussian convolution was further applied for the signal processing and hereby, the hotspots for all the windings and iron cores could be accurately traced. The hottest points were located at 89.1% (55 °C) of the high voltage winding height and 89.7% (77.5 °C) of the low voltage winding height. The actual precise hotspot location corrected the traditional cognition on the transformer windings and it would serve as an essential reference for the manufactures. This new nondestructive internal sensing and condition monitoring method also exhibits a promising future for the DFOS applying in the high-voltage electrical apparatus industry.

Transformer Winding Deformation Detection Based on BOTDR and ROTDR.

In order to realize distributed measurement of transformer winding temperature and deformation, a transformer winding modification scheme with a built-in distributed optical fiber was designed. By laying a single-mode fiber and a multi-mode fiber on the transformer winding, the Brillouin optical time domain reflection technique (BOTDR) and the Raman optical time domain reflection technique (ROTDR) are used to measure the strain and temperature of the winding to complete the more accurate winding deformation detection. The accuracy of strain and temperature sensing of this scheme was verified by simulation. Then, according to the scheme, a winding model was actually wound, and the deformation and temperature rise tests were carried out. The test results show that this scheme can not only realize the deformation detection and positioning of the winding, but can also realize the measurement of the winding temperature; the temperature measurement accuracy reached ±0.5 °C, the strain measurement accuracy was 200 µÎµ, and spatial resolution was up to 5 m. In this experiment, the deformation location with the precision of 2 turns was realized on the experimental winding.

Distributed temperature detection of transformer windings with externally applied distributed optical fiber.

The local overheating fault of power transformer winding threatens the safe, stable operation of a power system. Conventional winding temperature detection methods are point-type temperature measurements, and the hotspot position and the temperature distribution on the winding cannot be accurately obtained. A distributed temperature measurement method of transformer winding based on Raman scattering was thus proposed, and a fiber composite winding model was designed. The influence of fiber on electric field distribution and temperature transfer in oil was simulated, and the insulation performance of fiber composite winding was studied. The distributed optical fiber temperature measurement platform was built, and a temperature sensing test was conducted. The results show that the distributed temperature detection system of transformer winding has high temperature sensing and positioning performance with temperature measurement error less than 1°C and positioning accuracy error within 1.2 m. This means that this method can satisfy the requirements of transformer winding temperature measurement and provide a new, to the best of our knowledge, approach for online monitoring of high-power equipment.

Design and Performance Test of Transformer Winding Optical Fibre Composite Wire Based on Raman Scattering.

Winding overheating is a common fault in a transformer. To detect the temperature, the most widely used method is a point-type measurement, but traditional measurement methods cannot obtain the whole temperature distribution in a transformer. Taking this into consideration, a new method with which to measure the temperature of transformer windings was proposed. Based on Raman scattering, a new fibre-optic composite winding model was developed. The feasibility of the model was verified by electrical as well as temperature, field simulation and power frequency resistance testing. To assess the practicality and accuracy of the new model, a distributed optical fibre temperature measurement platform was built, and a series of experiments were designed. According to the data collected, the temperature measurement error based on the method could be limited to 1 °C while the positioning accuracy error was within 1 m, which meant that the new approach can satisfy the requirements of transformer winding temperature measurement and locate hot spots in the winding.

Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.

OBJECTIVE: A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. DESIGN: We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression. RESULTS: Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study. CONCLUSIONS: This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.

Detection and identification of transformer winding strain based on distributed optical fiber sensing.

At present, transformer winding strain monitoring is divided mainly into off-line detection and on-line detection. Due to the interference of the complex electromagnetic environment, on-line detection has not been widely used. Although off-line detection is more mature, it can not accurately judge the winding strain form. Based on the above problems, this research investigated a strain gauge strain detection method based on distributed fiber optic sensing, and proposes a winding strain identification method based on the S-transform and an extreme learning machine (ELM). First, the deformation of the winding in the process of transformer operation is simulated, and the corresponding Brillouin frequency shift is collected. Then, the time-frequency analysis of the strain signal is carried out using an S-transform, and the transformed time-frequency feature is extracted as the input sample to the neural network. An ELM was used for training identification. Experimental results show that the method can effectively identify the common winding deformation form, and that the recognition effect is better and the accuracy is high.

A Feasibility Study of Transformer Winding Temperature and Strain Detection Based on Distributed Optical Fibre Sensors.

The temperature distribution and deformation of the transformer windings cannot be measured in a distributed manner by the traditional method and failure location cannot be performed. To solve these problems, we present a transformer winding temperature and strain based on a distributed optical fibre sensing detection method. The design of the optical fibre winding composite model is developed and simulated winding temperature rise test and local deformation test distinguish between measuring the winding temperature and the strain curve. The test results show that the distributed optical fibre can transmit wire strain efficiently. Optical fibres, in the process of winding, have a certain pre-stress. Using the Brillouin⁻Raman joint measuring method, one can effectively extract the optical fibre temperature and strain information and measure the length of the winding direction of the temperature and strain distribution curve to a temperature measurement precision of ±2 °C and strain detection accuracy of ±50 µÎµ. The system can carry out local hot spot and deformation localisation, providing new ideas for the transformer winding state monitoring technology.

Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various organs.

BACKGROUND: Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it's a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated. RESULTS: The mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P < 0.05). Peak intensity and duration time of targeted nanobubbles and blank nanobubbles were different in CAIX-positive transplanted tumor tissues in vivo (P < 0.05). Moreover, targeted nanobubbles in CAIX-positive transplanted tumor tissues produced higher peak intensity and longer duration time than those in CAIX-negative transplanted tumor tissues (P < 0.05). Finally, immunofluorescence not only confirmed targeted nanobubbles could pass through blood vessels to enter in tumor tissue spaces, but also clarified imaging differences of targeted nanobubbles in different types of transplanted tumor tissues. CONCLUSIONS: Targeted nanobubbles carrying CAIX polypeptides can specifically enhance ultrasound imaging in CAIX-positive transplanted tumor tissues and could potentially be used in early diagnosis of a variety of solid tumors derived from various organs.

Safety of Sulfur Hexafluoride Microbubbles in Sonography of Abdominal and Superficial Organs: Retrospective Analysis of 30,222 Cases.

OBJECTIVES: The purpose of this study was to investigate the safety of the sulfur hexafluoride microbubble contrast agent SonoVue (Bracco SpA, Milan, Italy) and to implement precautions with the intent of further improving the safety of this contrast agent. METHODS: A total of 30,222 patients undergoing contrast-enhanced sonography of abdominal and superficial organs in our hospital from January 2005 to December 2014 were retrospectively investigated. SonoVue was used as the ultrasound contrast agent. The symptoms and treatments of adverse reactions occurring during the contrast-enhanced sonographic examinations were reviewed and analyzed. RESULTS: No patient died as a result of any adverse reaction. Six patients (0.020%) had adverse reactions of varying degrees, including 2 patients (0.007%) who had signs of early anaphylactic shock (chest tightness, palpitations, sweating, and rapid and weak pulse, followed by cyanosis, a disappearing pulse, and a drop in blood pressure) that improved after active rescue. The remaining 4 patients developed the following: redness and a rash on the arm above the injection site, nasal bleeding and nausea, nausea and vomiting, and back pain with numbness of the lips and limbs. Symptoms in these 4 patients self-resolved after a period of rest. CONCLUSIONS: Contrast-enhanced sonography with sulfur hexafluoride microbubbles had good clinical safety, but rare adverse reactions were observed. A comprehensive emergency plan and rescue measures for adverse reactions should be prepared and made available to minimize the occurrence of negative clinical outcomes.

Age at cancer diagnosis, amenability to medical interventions, and racial/ethnic disparities in cancer mortality.

PURPOSE: Racial disparities in cancer mortality may be greater for cancers that are amenable to available early detection and treatment (amenability level). We investigated whether these patterns vary by age at cancer diagnosis. METHODS: Using 5-year relative survival rates (5Y-RSR), we classified 51 cancer sites into least amenable, partly amenable, and mostly amenable cancers (<40%, 40-69%, ≥70% 5-YRS, respectively). We examined whether racial disparities in mortality rates (African-Americans, Asian/Pacific Islanders, Hispanics, whites), as estimated through Cox regression models, were modified by age at diagnosis and amenability level in 516,939 cancer cases diagnosed in 1995-1999. RESULTS: As compared with whites, all racial minority groups experienced higher cancer mortality rates in the youngest age group of 20-34 years. African-Americans and Hispanics diagnosed with partly and mostly amenable cancers had higher mortality rates relative to whites with cancers of the same amenability levels; further, these differences decreased in magnitude or reversed in direction with increasing age. In contrast, the racial differences in mortality were smaller and remained fairly constant across age groups for least amenable cancers. For example, in the youngest (20-34) and oldest (80-99) age groups, the adjusted hazard ratios (HRs) for African-Americans versus whites with least amenable cancers were, respectively, 1.26 (95% CI 1.02, 1.55) and 0.90 (95% CI 0.85, 0.96), while the HRs for African-Americans versus whites with mostly amenable cancers were 2.77 (95% CI 2.38, 3.22) and 1.07 (95% CI 0.98, 1.17). CONCLUSIONS: Cancer survival disadvantage for racial minorities is larger in younger age groups for cancers that are more amenable to medical interventions.

Use of FOLFOXIRI Plus Bevacizumab and Subsequent Therapies in Metastatic Colorectal Cancer: An Age-Stratified Analysis.

BACKGROUND: Treatment recommendations for metastatic colorectal cancer (mCRC) do not differ by age group; nevertheless, aggressive multiagent chemotherapy comprising FOLFOXIRI+bevacizumab (triplet+bev) is routinely administered in younger patients. This study analyzed real-world data on index triplet+bev use and subsequent systemic therapies. MATERIALS AND METHODS: This retrospective, observational cohort study was conducted in patients aged ≥ 18 years with mCRC, who were initiated on triplet+bev. Data were derived from the Optum de-identified electronic health record dataset. RESULTS: Of 36,056 patients, 14%, 36%, and 50% were aged 18-49, 50-64, and ≥ 65 years, respectively. During the study period (2010-2021), triplet+bev use increased in patients aged 18-49 years (1%-4%) but remained at approximately 3% and 1% in patients aged 50-64 and ≥ 65 years, respectively. Patient demographics and clinical characteristics varied slightly; of patients receiving triplet+bev (n = 921) versus nontriplet+bev (n = 35,132) most were male (57% vs. 52%), resided in the Midwest (54% vs. 49%) and Northeast (18% vs. 14%) US regions, and had secondary malignancies (86% vs. 73%). Following triplet+bev, most patients received subsequent therapies (including continued triplet component therapies; 97%) or subsequent "new" therapies (therapies that did not include any agents comprising triplet+bev; 57%), most frequently EGFR inhibitors (28%) and regorafenib (21%), with a similar trend among all age groups. CONCLUSIONS: Overall, this study shows that younger patients with mCRC are more likely to receive first-line triplet+bev. These results also reveal that nonchemotherapy options are often used beyond first-line triplet chemotherapy for patients with mCRC.

ICOS costimulation in combination with CTLA-4 blockade remodels tumor-associated macrophages toward an antitumor phenotype.

We have previously demonstrated synergy between ICOS costimulation (IVAX; ICOSL-transduced B16-F10 cellular vaccine) and CTLA-4 blockade in antitumor therapy. In this study, we employed CyTOF and single-cell RNA sequencing and observed significant remodeling of the lymphoid and myeloid compartments in combination therapy. Compared with anti-CTLA-4 monotherapy, the combination therapy enriched Th1 CD4 T cells, effector CD8 T cells, and M1-like antitumor proinflammatory macrophages. These macrophages were critical to the therapeutic efficacy of anti-CTLA-4 combined with IVAX or anti-PD-1. Macrophage depletion with clodronate reduced the tumor-infiltrating effector CD4 and CD8 T cells, impairing their antitumor functions. Furthermore, the recruitment and polarization of M1-like macrophages required IFN-γ. Therefore, in this study, we show that there is a positive feedback loop between intratumoral effector T cells and tumor-associated macrophages (TAMs), in which the IFN-γ produced by the T cells polarizes the TAMs into M1-like phenotype, and the TAMs, in turn, reshape the tumor microenvironment to facilitate T cell infiltration, immune function, and tumor rejection.

Altered salivary microbiota associated with high-sugar beverage consumption.

The human oral microbiome may alter oral and systemic disease risk. Consuming high sugar content beverages (HSB) can lead to caries development by altering the microbial composition in dental plaque, but little is known regarding HSB-specific oral microbial alterations. Therefore, we conducted a large, population-based study to examine associations of HSB intake with oral microbiome diversity and composition. Using mouthwash samples of 989 individuals in two nationwide U.S. cohorts, bacterial 16S rRNA genes were amplified, sequenced, and assigned to bacterial taxa. HSB intake was quantified from food frequency questionnaires as low (< 1 serving/week), medium (1-3 servings/week), or high (> 3 servings/week). We assessed overall bacterial diversity and presence of specific taxa with respect to HSB intake in each cohort separately and combined in a meta-analysis. Consistently in the two cohorts, we found lower species richness in high HSB consumers (> 3 cans/week) (p = 0.027), and that overall bacterial community profiles differed from those of non-consumers (PERMANOVA p = 0.040). Specifically, presence of a network of commensal bacteria (Lachnospiraceae, Peptostreptococcaceae, and Alloprevotella rava) was less common in high compared to non-consumers, as were other species including Campylobacter showae, Prevotella oulorum, and Mycoplasma faucium. Presence of acidogenic bacteria Bifodobacteriaceae and Lactobacillus rhamnosus was more common in high consumers. Abundance of Fusobacteriales and its genus Leptotrichia, Lachnoanaerobaculum sp., and Campylobacter were lower with higher HSB consumption, and their abundances were correlated. No significant interaction was found for these associations with diabetic status or with microbial markers for caries (S. mutans) and periodontitis (P. gingivalis). Our results suggest that soft drink intake may alter the salivary microbiota, with consistent results across two independent cohorts. The observed perturbations of overrepresented acidogenic bacteria and underrepresented commensal bacteria in high HSB consumers may have implications for oral and systemic disease risk.

Construction and in vitro/in vivo targeting of PSMA-targeted nanoscale microbubbles in prostate cancer.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a highly specific biological marker and treatment target for prostate cancer. So ultrasound molecular imaging using PSMA antibody-loaded targeted nanoscale microbubbles (MBs) may contribute to the early diagnosis of prostate cancer. METHODS: PSMA monoclonal antibody-loaded targeted nanoscale MBs were prepared using biotin-avidin technology. Antibody binding was evaluated with immunofluorescence. Using MKN45 gastric cancer cells as controls, the targeting capability of the targeted MBs was observed in prostate cancer cells (LNCaP and C4-2) under optical microscope. Contrast enhancement was monitored by an ultrasound system in C4-2, LNCaP, and MKN45 transplanted tumors in nude mice. The arrival time, time to peak, peak intensity, and duration of contrast enhancement of targeted and blank nanoscale MBs were compared and analyzed. RESULTS: Targeted PSMA monoclonal antibody-loaded nanoscale MBs were successfully synthesized. These MBs were stable and could specifically bind to LNCaP and C4-2 cells in vitro but did not bind to MKN45 cells. There were significant differences in peak intensity and duration of contrast enhancement between targeted and blank nanoscale MBs in both transplanted prostate tumors (P < 0.05). Among the three types of transplanted tumors with targeted nanoscale MBs, the peak intensity was significantly higher in prostate tumors (LNCaP and C4-2) than in gastric tumors (MKN45) (P < 0.05). CONCLUSIONS: PSMA monoclonal antibody-loaded targeted nanoscale MBs can target and bind to prostate cancer cells specifically and allow for obvious contrast enhancement in vivo. Therefore, this study lays a foundation for early diagnosis and targeted therapy for prostate cancer.

Experimental investigation of the penetration of ultrasound nanobubbles in a gastric cancer xenograft.

Nanobubbles as a type of ultrasound contrast agent have attracted much interest in recent years due to their many advantages, such as strong penetrating power and high stability. However, there is still insufficient morphological evidence concerning gas-filled nanobubbles in tumor tissue spaces and tumor angiogenesis. We used a gastric cancer xenograft as an example to study this question. Nanobubbles with a particle size of 435.2 ± 60.53 nm were prepared and compared with SonoVue® microbubbles in vitro and in vivo, and they exhibited a superior contrast imaging effect. After excluding the impact of the nanobubbles in blood vessels through saline flush, we used an ultrasound burst and frozen sectioning to investigate the distribution of nanobubbles in the gastric cancer xenografts and confirmed this by transmission electron microscopy. Preliminary results showed that the nanobubbles were able to pass through the gaps between the endothelial cells in the tumor vascular system to enter the tissue space. These findings could provide morphological evidence for extravascular ultrasound imaging of tumors and serve as a foundation for the application of nanobubbles in extravascular tumor-targeted ultrasonic diagnostics and therapy.