Tungsten-based nanoparticles as contrast agents for liver tumor detection using dual-energy computed tomography.

Dual-energy computed tomography (DECT) is a commonly used imaging technique for detecting and diagnosing liver cancer. Currently, it is performed using clinically approved iodinated small molecule contrast agents (CAs). However, these iodinated CAs have several drawbacks, including sub-optimal contrast generation and contra-indication in patients with renal insufficiency. Herein, we synthesized tungsten-based CAs (i.e., WO3-x NPs) with excellent biocompatibility and investigated their effectiveness in DECT imaging. WO3-x NPs significantly enhanced the contrast between liver tumors and normal liver tissues as indicated by in vivo DECT imaging. Furthermore, WO3-x NPs exhibited excellent biocompatibility and minimal systemic toxicity. This study introduces a novel class of CAs for DECT and presents a promising method for accurate early diagnosis of liver tumors.

Covered stent treatment for arterial complications after pancreatic surgery: risk assessment for recurrence and peri-stent implantation management.

OBJECTIVES: To explore the risk factors for recurrence of arterial complications after pancreatectomy during the period of covered stent implantation and to provide some opinions on peri-stent implantation management. METHODS: Data on patients implanted with covered stents due to arterial complications after pancreatectomy between January 2017 and December 2021 were analyzed retrospectively. Technical success, clinical success, recurrence, and survival were evaluated to elucidate the practicability of covered stents. Wilson score, Random Forest, logistic regression, and Pearson's chi-square test with bootstrap aggregation were performed for determining the perioperative risk factors for recurrence. RESULTS: Among all fifty-five patients, success stent implantation (technical success) was achieved 100%. Patients who were hemodynamically stabilized without further treatment for artery complications in situ (clinical success) accounted for 89.1%. Based on statistical analysis, pre-stent implantation pancreatic fistula was identified as a robust recurrence-related risk factor for preoperative assessment (p = 0.02, OR = 4.5, 95% CI [1.2, 16.9]; pbootstrap = 0.02). Post-stent implantation pancreatic fistula (p = 0.01, OR 4.5, 95% CI [1.4, 14.6]; pbootstrap < 0.05) and SMA branches or GDA stumps (p = 0.02, OR 3.4, 95% CI [1.1, 10.3]) were relevant to recurrence. The survival rate during hospitalization was 87.3%. All survivors were free from recurrence during the subsequent follow-up. Vasospasm and stent occlusion were observed as short-term and long-term complications, respectively. CONCLUSION: A covered stent implantation is a feasible and effective treatment option for post-pancreatectomy arterial complications. Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis. KEY POINTS: • A covered stent is feasible for various artery-related complications after pancreatectomy and has an ideal therapeutic effect. • Pancreatic fistula during the perioperative period of the covered stent is an independent risk factor for recurrent arterial complications and SMA branches or GDA stumps are prone to be recurrent offending arteries. • Rigorous management of pancreatic fistula, timely detection of problems, sensible strategies during stent implantation, and reasonable anticoagulation therapy are necessary for a better prognosis.

Evaluation of D-TACE combined with endovascular brachytherapy for HCC with MPVTT.

Background: Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT) may be able to have TACE through stent implantation into the portal vein with thrombosis to recover portal blood flow. Purpose: The goal of this study was to compare clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular brachytherapy in HCC patients with MPVTT. Methods: This study was a retrospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. Results: A total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p=0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p=0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times. Conclusion: Endovascular implantation of brachytherapy combined with TACE is safe and effective in HCC patients with MPVTT. This combination therapy may be helpful for survival benefits to patients with stage BCLC-C HCC.

Percutaneous Ablation of Hepatic Tumors at the Hepatocaval Confluence Using Irreversible Electroporation: A Preliminary Study.

BACKGROUND: Tumors at the hepatocaval confluence are difficult to treat, either surgically or ablatively. METHODS: A retrospective longitudinal study on patients ineligible for thermal ablation who underwent computed tomography-guided IRE for hepatic tumors at the hepatocaval confluence was conducted. Factors analyzed included patient and tumor characteristics, IRE procedure details, treatment-related complications, and prognosis. RESULTS: Between 2017 and 2021, 21 patients at our institute received percutaneous IRE. Of the 38 lesions, 21 were at the hepatocaval confluence. Complete ablation was achieved in all cases. Local and distant recurrence was observed in 4.8% (1/21) and 42.6% (9/21) of the ablated tumors, respectively. All postcava remained perfused at follow-up, except for 1 (4.8%) hepatic vein near the lesion found to be temporarily occluded and restored within 1 month. The ratio of the maximum diameter of ablation area at 1, 3, and 6 months post procedure compared to that immediately after IRE was 0.68 (0.50-0.84), 0.49 (0.27-0.61), and 0.38 (0.25-0.59), respectively. Progression-free survival of the patients with recurrence was 121 (range, 25-566) days. Four (19.0%) patients died at the end of follow-up with median overall survival of 451.5 (range, 25-716) days. CONCLUSIONS: IRE could be a safe and effective treatment for hepatic tumors at the hepatocaval confluence. This article provides valuable prognostic data; further clinical research is needed for better prognosis.

An NIR-II Photothermally Triggered "Oxygen Bomb" for Hypoxic Tumor Programmed Cascade Therapy.

Hypoxia, as a characteristic feature of solid tumors, has a close relationship with tumor resistance to photodynamic therapy (PDT) and chemotherapy. Perfluorocarbon (PFC) is reported to relieve hypoxic in solid tumors by acting as an oxygen carrier via several nanostructures. However, the oxygen delivery process is mostly driven by a concentration gradient, which is uncontrollable. Herein, a photothermally controlled "oxygen bomb" PSPP-Au980 -D is designed by encapsulating a PFC core within a functionalized bilayer polymer shell. Near-infrared second window photothermal agent gold nanorods with excellent photo-to-heat energy-conversion ability are fabricated on the surface of the polymer shell via an innovative modified two-step seedless ex situ growth process to thermally trigger O2  release. Then, a programmed cascade therapy strategy is customized for hypoxic orthotopic pancreatic cancer. First, PSPP-Au980 -D is irradiated by a 980 nm laser to photothermally trigger O2  infusing into the hypoxic tumor microenvironment, which is accompanied by local hyperemia and doxorubicin release. Subsequently, a 680 nm laser is used to generate singlet oxygen in the oxygenated tumor microenvironment for PDT. This choreographed programmed cascade therapy strategy will provide a new route for suppressing hypoxic tumor growth under mild conditions based on controllable and effective oxygen release.

A fluorescent microsphere-based immunochromatographic strip is effective for quantitative fecal blood testing in colorectal cancer screening.

Background: Colorectal cancer (CRC) represents a major health concern that can be screened for by the fecal immunochemical test (FIT), which detects blood in the stool. CRC detection sensitivity for hemoglobin (Hb) combined with transferrin (Tf) is higher than for hemoglobin alone. Methods: We developed a europium fluorescent microsphere-based quantitative lateral flow immunochromatography strip to detect fecal Hb and Tf. Performance was tested using fecal samples from 51 patients with CRC and 122 normal subjects. Test strips were generated using paired mouse anti-human Hb and mouse anti-human Tf monoclonal antibodies and tested using standard Hb and Tf samples. Fluorescence was observed at 365 nm and quantitatively measured using a portable fluorescent strip reader. Results: At cutoff values of 100 ng/mL (10 µg/g feces) and 25 ng/mL (2.5 µg/g feces) for Hb and Tf, respectively, the positive rates for Hb, Tf, and Hb+Tf in normal subjects were 6.56%, 5.74%, and 10.66%, respectively, compared to 88.24%, 64.71%, and 94.12% in patients with CRC. The sensitivity and specificity of the FIT combined detection technique were 87.5% and 89.2%, respectively, and the area under the curve (AUC) was 0.92. The sensitivity, specificity, and AUC for the Tf assay were 63.8%, 68.4%, and 0.759, respectively, and those for Hb testing were 69.7%, 70.2%, and 0.774, respectively. The AUC for Hb+Tf was significantly higher than those for Tf or Hb alone (P < 0.001). Conclusions: Fluorescent microsphere-based immunochromatographic strips sensitively detect fecal Hb and Tf, and sensitivity and specificity are improved for Hb+Tf. This system represents a rapid and portable alternative for on-site early CRC screening.

Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment.

Pancreatic ductal adenocarcinoma (PDAC) is on of the most lethal malignant tumors with relatively poor prognosis, characterized with insufficient drug penetration, low immune response and obvious drug resistances. The therapeutic inefficiency is multifactorially related to its specific tumor microenvironment (TME), which is representatively featured as rich stroma and immunosuppression. In this work, a versatile drug delivery system is developed that can coencapsulate two prodrugs modified from gemcitabine (GEM) and a signal transducer and activator of transcription 3 (STAT3) inhibitor (HJC0152), and the gradient pH variation is further sensed in the TME of PDAC to achieve a higher penetration by reversing its surficial charges. The escorted prodrugs can release GEM intracellularly, and respond to the hypoxic condition to yield the parental STAT3 inhibitor HJC0152, respectively. By inhibiting STAT3, the tumor immunosuppression microenvironment can be re-educated through the reversion of M2-like tumor associated macrophages (M2-TAMs), recruitment of cytotoxic T lymphocytes and downregulation of regulatory T cells (Treg s). Furthermore, cytidine deaminase (CDA) and α-smooth muscle actin (α-SMA) expression can be downregulated, plus the lipid modification of GEM, the drug resistance of GEM can be greatly relieved. Based on the above design, a synergetic therapeutic efficacy in PDAC treatment can be achieved to provide more opportunity for clinical applications.

A panel of epigenetically dysregulated Wnt signaling pathway genes for non-invasive diagnosis of pediatric acute lymphoblastic leukemia.

BACKGROUND: Genetic and epigenetic dysregulation of Wnt signaling pathway is widely linked up with abnormal proliferation and/or epithelial-to-mesenchymal transition, in different cancer cell types. OBJECTIVE: In the present research, we have tested whether promoter DNA methylation of a set of Wnt/non-Wnt genes such as [cadherin-2 (CDH2)], "present in circulation", could serve as "bone-marrow biopsy surrogate" and help in diagnosing the status, sub-type or treatment outcome in pediatric acute lymphoblastic leukemia (ALL) patients. METHODS: Promoter DNA methylation was quantified in the bisulfite modified blood from the pediatric ALL patients (n= 86) in comparison with age-matched cancer-free subjects (n= 28), using real-time methylation specific PCR followed by rigorous statistical validations. RESULTS: The observed methylation index, sensitivity and specificity of selected molecular markers (viz., SALL1, WNT5α, LRP1b, CDH2) in patients' liquid-biopsies was clinically significant showing high positive correlation in the pre-B ALL cases (p-value < 0.001). A substantial drop in promoter methylation signal of the follow-up/post-treatment patients was also noted (p-value < 0.001), which suggested an impending role of minimally invasive liquid-biopsy approach in the diagnosis and/or therapeutic monitoring of pediatric leukemia. CONCLUSIONS: Whilst the reported metadata provides useful insight into the plausible involvement of epigenetic glitches in leukemogensis, our findings strengthen the remarkable functional consequences of dysregulated Wnt signaling genes in the hematological malignancies besides offering a novel panel of epigenetic marks.

OX40 agonist combined with irreversible electroporation synergistically eradicates established tumors and drives systemic antitumor immune response in a syngeneic pancreatic cancer model.

In this study, we intended to explore a novel combination treatment scheme for pancreatic cancer, using irreversible electroporation (IRE) and OX40 agonist. We further aimed to investigate the capacity and mechanism of this combination treatment using an in vivo mouse aggressive pancreatic cancer model. To this end, mice subcutaneously injected with KPC1199 pancreatic tumor cells were treated with IRE, followed by intraperitoneal injection of OX40 agonist. Tumor growth and animal survival were observed. Flow cytometry analysis, immunohistochemistry, and immunofluorescence were used to evaluate the immune cell populations within the tumors. The tumor-specific immunity was assessed using ELISpot assay. Besides, the cytokine patterns both in serum and tumors were identified using Luminex assay. After combination therapy with IRE and OX40 agonist, 80% of the mice completely eradicated the established subcutaneous tumors, during the 120 days observation period. Rechallenging these tumor-free mice at day 120 with KPC1199 tumor cells leads to complete resistance to tumor growth, suggesting that the combination therapy generated long-term-specific antitumor immune memory. Moreover, combination therapy significantly delayed the growth of contralateral untreated tumors, and significantly prolonged animal survival, suggesting that a potent systematic anti-tumor immunity was induced by combination therapy. Mechanically, combination therapy amplified antitumor immune response induced by IRE, as manifested by the increased quality and quantity of CD8+ T cells trigged by IRE. Together, these results provide strong evidence for the clinical assessment of the combination of IRE and OX40 agonist in patients with pancreatic cancer.

Risk factors for developing high-output ileostomy in CRC patients: a retrospective study.

BACKGROUND: Anastomotic leakage is one of the most serious postoperative complications of rectal cancer. Prophylactic ileostomy has been widely used to reduce the risk and severity of complications of anastomotic leakage. However, prophylactic ileostomy itself has some complications, and ileostomy high output syndrome (HOS) is one of them. This study was performed to explore the risk factors of HOS in ileostomy. METHODS: A total of 114 patients with HOS were screened out from 494 eligible ileostomy patients in the last 5 years. The relationship between HOS and the clinicopathological data was analyzed using the Chi-square test and Fisher's exact probability. Multivariate analysis was performed by logistic regression. RESULTS: The incidence of HOS was 23.07% in this study. Dehydration was the most common symptom of HOS (37.7%). There was no clear correlation between HOS occurrence with sex, age, gross typing, histological grade, tumor location, lymph node metastasis, and TNM stage (p > 0.05). The incidence of HOS was 14/18 in inflammatory bowel disease patients, 18/28 in diabetes mellitus patients, and 23/72 in neoadjuvant chemoradiotherapy patients, 13/17 in total colectomy and abdominal infection patients. Multivariate analysis showed that they are risk factors for HOS (p < 0.05). CONCLUSION: HOS occurred occasionally but rarely studied and lacks attention. Inflammatory bowel disease, diabetes mellitus, neoadjuvant radiotherapy chemotherapy, total colectomy and abdominal infection are the risk factors for HOS.

Immunological effect of irreversible electroporation on hepatocellular carcinoma.

BACKGROUND: This study intends to investigate the immunological effects of tumor ablation with irreversible electroporation (IRE). METHODS: We evaluated the systemic immune response in patients with hepatocellular carcinoma (HCC) after IRE treatment. Furthermore, we analyzed the tumor infiltrating T lymphocytes and the level of serum cytokines in IRE and control groups of tumor-bearing mice. RESULTS: We observed that IRE induced an increase in WBC, neutrophil and monocyte counts and a decrease in lymphocyte count 1 day post-IRE and returned to baseline values within 7 days in the patients. Meanwhile, circulating CD4+ T cell subsets, but not CD8+, decreased 1 day post-IRE. The activated T cells and natural killer (NK) cells increased, and regulatory T (Treg) cells decreased. Furthermore, a significant increase in cytotoxic CD8+ T cells infiltration was observed on ablative tumors in mice. The level of serum IFN-γ also significantly increased in the IRE group. CONCLUSIONS: Our study demonstrated that IRE upregulated activated T cells and downregulated Tregs in the peripheral blood of patients. Meanwhile, the results from the animal model indicated that IRE could induce antitumor adaptive immunity dominated by the infiltration of cytotoxic CD8+ T cells into the tumors, accompanied by reduced Tregs.

A retrospective study of CT-guided percutaneous irreversible electroporation (IRE) ablation: clinical efficacy and safety.

BACKGROUND: To evaluate the clinical efficacy and safety of ablating renal cell carcinoma (RCC) by irreversible electroporation (IRE). METHODS: Fifteen patients (19 lesions) with RCC who underwent IRE were retrospectively reviewed. Seven patients had solitary kidneys. Two lesions were located in the renal hilus. One patient had chronic renal insufficiency. Percutaneous biopsy for histopathology was performed. The best puncture path plan was evaluated before CT-guided IRE. The estimated glomerular filtration rate (eGFR) was compared vs baseline at 1-2 months after the ablation. Contrast-enhanced computed tomography imaging changes were evaluated immediately after IRE. Contrast-enhanced computed tomography/magnetic resonance was performed 1 month, 3 months, 6 months, 12 months and every year thereafter. The complications after treatment were also reviewed. RESULTS: The success rate of the procedure was 100%. The median tumor size was 2.4 (IQR 1.3-2.9) cm, with an median score of 6 (IQR 5.5-8) per R.E.N.A.L. criteria (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, and location relative to polar lines). Two cases (3 lesions) were punctured through the liver. In other cases, puncture was performed through the perirenal space. There were no severecomplications in interventional therapy. Transient gross hematuria occurred in 2 patients (centrally located). Self-limiting perinephric hematomas occurred in 1 patient. Needle puncture path metastasis was found in 1 patient 2.5 years after IRE. The subcutaneous metastasis was surgically removed, and there was no evidence of recurrence. There was no significant change in eGFR levels in terms of short- term clinical outcomes (t = 0.348, P = 0.733). At 6 months, all 15 patients with imaging studies available had no evidence of recurrence. At 1 year, 1 patient (1 of 15) was noted to have experienced needle tract metastasis and accepted salvage radiofrequency ablation (RFA) therapy. CONCLUSIONS: IRE appears to be a safe and effective treatment for RCC that may offer a tissue-sparing method and complete ablation as an alternative therapy for RCC.

SUMO-fusion and autoinduction-based combinatorial approach for enhanced production of bioactive human interleukin-24 in Escherichia coli.

High-level production of recombinant human interleukin-24 (IL-24), a multifunctional immunomodulatory cytokine, has been challenging due primarily to its aggregation as inclusion bodies in the bacterial host while persistent poor-expression in the insect/mammalian expression systems. The present study presents a robust, vector-host combination (pE-SUMO-IL24), auto-inducible medium (YNG/M9NG), and a simple purification scheme for soluble, bioactive, and cost-effective production of native-like IL-24 (nIL-24) in Escherichia coli. The final protein yield, following a three-step purification scheme (IMAC, SEC, dialysis), was 98 mg/L in shake-flask culture (with scale-up potential), which was several folds higher than reported earlier. In vitro cytotoxicity assays with HeLa and HCT116 cancer cell lines (performed using different concentrations of nIL-24) and the fluorescence activated cell sorting analysis (FACS) revealed a dose- and concentration-dependent increase in the population of pro-apoptotic cells with concomitant, statistically significant drop in the number of cells existent at Go/G1-, S-, and G2/M-phases (P < 0.002). The bioactive nIL-24, developed through this study, holds promise for use in further functional characterizations/applications. KEY POINTS: • Yeast SUMO fusion partner at N-terminus for improved solubility of an otherwise insoluble IL-24 in E. coli. • Enhanced cell densities with concomitant several-fold increase in protein yield by lactose-inducible media. • Improved inhibition of cervical and colorectal carcinomas by native-like nIL-24 compared with Met-containing IL. • Heterologous nIL-24 may enable better understanding of the functional intricacies linked up with its unique cancer-specific features. Graphical abstract.

Bone marrow mesenchymal stem cells-derived exosomes for penetrating and targeted chemotherapy of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix (ECM). Based on the theory that bone marrow mesenchymal stem cells (BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes (Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel (PTX) and gemcitabine monophosphate (GEMP)-an intermediate product of gemcitabine metabolism-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy in vivo and in vitro, plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance (Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.

Phase Contrast Imaging Based Microbubble Monitoring of Radiofrequency Ablation: An ex vivo Study.

BACKGROUND: To explore the potential of synchrotron radiation (SR) phase contrast imaging (PCI) for real-time microbubble formation monitoring during radiofrequency ablation (RFA). METHODS: RFA was performed on ex vivo porcine muscle tissue using unipolar and multi-tined expandable electrodes. Images of microbubble formation in the samples were captured by both SR PCI and absorption contrast imaging. The synchronous ablation temperature was recorded. Each RFA electrode type group contained 6 samples. Ablation size was assessed by histologic examination. RESULTS: Microbubble formation during RFA could be visualized by SR PCI. The diameter of the microbubbles revealed on the image ranged from tens of microns to several millimeters, and these microbubbles first appeared at the edge of the RFA electrode when the target region temperature reached approximately 60°C and rapidly extended outwards. The average microbubble range measured on PCI was 17.66 ± 0.74 mm. The average range of coagulation necrosis measured by histological examination was 17.22 ± 0.38 mm. There was no significant difference between them (P > 0.05). The range of microbubbles corresponded to the ablation zone. CONCLUSION: PCI enabled real-time high-resolution visualization of microbubble formation during RFA, indicating a potential for its use in ablation monitoring.

Quantitative Mapping of Liver Hypoxia in Living Mice Using Time-Resolved Wide-Field Phosphorescence Lifetime Imaging.

Hypoxia has been identified to contribute the pathogenesis of a wide range of liver diseases, and therefore, quantitative mapping of liver hypoxia is important for providing critical information in the diagnosis and treatment of hepatic diseases. However, the existing imaging methods are unsuitable to quantitatively assess liver hypoxia due to the need of liver-specific contrast agents and be easily affected by other imaging factors. Here, a time-resolved lifetime-based imaging method is established for quantitative mapping of the distribution of hypoxia in the livers of mice by combining a wide-field luminescence lifetime imaging system with an oxygen-sensitive nanoprobe. It is shown that the method is suitable for real-time quantification of the change of oxygen pressure in the process of hepatic ischemia-reperfusion of the mouse. Moreover, the developed lifetime imaging methodology is used to quantitatively map liver hypoxia regions in the mouse model of orthotopic liver tumor, where the average oxygen pressure in tumorous liver is far below the normal liver.

Theranostics system caged in human serum albumin as a therapy for breast tumors.

Biomimetic materials are attracting increasing attention in the field of drug delivery due to their low immunogenicity, good biocompatibility and degradability. Furthermore, the modification of endogenous species on the surfaces of biomimetic materials can generate new biomedical functions. A real-time understanding of the drug-release behavior, especially in vivo, can provide reliable information for drug activation and distribution. Herein, we describe a theranostics system caged in human serum albumin (HSA) as a therapy against breast tumors. The prodrug of a drug-dye conjugate (DDC) was successfully covalently linked into HSA via a disulfide-exchange reaction to give a high drug-loading rate. The drug-release and fluorescence recovery curves are in good agreement, allowing the drug-release kinetics to be monitored by a non-invasive fluorescence signal in real time. A disintegration mechanism triggered by GSH was suggested. The DDC@HSA particles show tumor-targeting capability, and good antitumor efficacy in vitro and in vivo. Hopefully, this strategy can provide a generalizable novel approach for the facile encapsulation of drugs for engaging HSA, paving the way for precision diagnosis and therapy in preclinical trials.

Thermally sensitive fluorescence imaging system for radiofrequency ablation guidance.

Radiofrequency ablation (RFA) has been clinically used as a minimally invasive procedure for the treatment of many solid tumors. However, the current imaging techniques have some shortages in RFA guidance, especially for the assessment of the margin of ablation. Herein, we developed a novel optical imaging platform to guide RFA utilizing fluorescence resonance energy transfer from a thermally sensitive fluorescent protein conjugated to a near-infrared fluorescent dye. Additionally, attaching receptor-targeting ligands further equipped the system with high specificity to tumors overexpressing the targeted receptor.

Determination of the optimal detection time of circulating tumor cells for the postoperative monitoring of colorectal cancer.

Circulating tumor cells (CTCs) are widely used in cancer screening and monitoring. The present study focused on investigating the optimal time for the postoperative CTC detection in patients with colorectal cancer (CRC) to obtain more accurate results and facilitate subsequent treatment. By subtraction enrichment immunofluorescence in situ hybridization detection of CTCs, the present study demonstrated that different postoperative detection times in CRC substantially influenced the CTC numbers. In total, 134 subjects were enrolled. Among 10 healthy individuals and 20 preoperative patients with CRC, no CTCs were identified in the healthy subjects, and CTCs were detected in 85% (17/20) of the preoperative patients. In total, 104 postoperative patients with CRC (53 males and 51 females) with a mean average age of 57.63 years were studied. The total CTC detection rate was 81.73% (85/104) and the mean average CTC numbers in patients with tumor stage (T) T1, T2, T3 and T4 were 4.00, 3.33, 5.90 and 5.64 per 7.50 ml of peripheral blood, respectively. The CTC number trends in these four tumor stages within 5, 6, 7 and 10 postoperative days were variable, and were the most stable at 7 days. Gradual upward trends in CTC numbers were observed after 5, 6 and 7 postoperative days, and this upward trend was more obvious after 7 days. Overall, the findings of the present study suggest that CTC detection in CRC should be performed after at least 7 postoperative days rather than within 7 postoperative days.

Theranostic nanoparticles enabling the release of phosphorylated gemcitabine for advanced pancreatic cancer therapy.

Gemcitabine (GEM) has been the recommended first-line drug for patients with pancreatic ductal adenocarcinoma cancer (PDAC) for the last twenty years. However, GEM-based treatment has failed in many patients because of the drug resistance acquired during tumorigenesis and development. To override resistance to GEM in pancreatic cancer, we developed a visualisable, photothermally controlled, drug release nanosystem (VPNS). This nanosystem has NaLuF4:Nd@NaLuF4 nanoparticles as the luminescent core, octabutoxyphthalocyanine palladium(ii) (PdPc) as the photothermal agent, and phosphorylated gemcitabine (pGEM) as the chemodrug. pGEM, one of the active forms of GEM, can circumvent the insufficient activation of GEM in cancer cell metabolism. The NaLuF4:Nd@NaLuF4 nanoparticles were employed to visualise the tumor lesion in vivo by their near-infrared luminescence. The near-infrared light-triggered photothermal effect from PdPc could trigger the release of pGEM loaded in a thermally responsive ligand and simultaneously enable photothermal cancer treatment. This work presents an effective method that suppresses the growth of tumour cells with dual-mode treatment and enables the improved treatment of orthotopic nude mice afflicted with pancreatic cancer.