A diagnosis based on multiple nuclear medicine imaging (NMI) was more comprehensive in approaching the nature of pathological changes. In this research, a method to realize triple NMIs within one day was developed based on the reasonable arrangements of 68Ga-RGD PET/CT specialized on neovascularization, 99mTc-HL-91 SPECT/CT specialized on hypoxia and 18F-FDG PET/CT specialized on tumor metabolism. Feasibility was verified in evaluating the therapeutic effects of transarterial embolization (TAE) performed on rabbit models with VX2 tumor. Radiation dosimetry was carried out to record the radiation exposure from multiple injections of radiopharmaceuticals. In results, the one-day examination of triple NMIs manifested the diversity of the postoperative histological changes, including the local neovascularization induced by embolization, hypoxic state of embolized tissues, and suppression of tumor metabolism. More importantly, radiation dosage from radiopharmaceuticals was limited below 5.70 ± 0.90 mSv. In conclusion, the strong timeliness and complementarity of one-day examination of triple nuclear medicine imaging made it clinically operative and worthy of popularizing. There was flexibility in combining distinct NMIs according to the clinical demands, so as to provide comprehensive information for diagnosis.
BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.
Thyroid Neoplasms , Thyroid Nodule , Humans , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/genetics , Prospective Studies , Artificial Intelligence , Ultrasonography , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Retrospective Studies
Betaine-homocysteine methyltransferase (BHMT) regulates protein methylation and is correlated with tumorigenesis; however, the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored. Here, we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma (HCC) using tissue samples from 198 patients. BHMT was to be frequently found (86.6%) expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC. Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo, whereas complete knockout of Bhmt (Bhmt-/-) produced the opposite effect. We combined proteomics, metabolomics, and molecular biological strategies and detected that Bhmt-/- promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models. In contrast, restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis. Additionally, coimmunoprecipitation identified monomethylated modifications of the G6PD, and BHMT regulated the methylation of G6PD. Protein sequence analysis, generation and application of specific antibodies, and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246. Furthermore, we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD, thereby inhibiting G6PD activity, which in turn suppressed hepatocarcinogenesis. Taken together, this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency, suggesting a potential therapeutic strategy for HCC treatment.
Derivative spectroscopy is used to separate the small absorption peaks superimposed on the main absorption band, which is widely adopted in modern spectral analysis to increase both the valid spectral information and the identification accuracy. In this study, a method based on attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) with first-order derivative (FD) processing combined with chemometrics is proposed for rapid qualitative and quantitative analysis of Panax ginseng polysaccharides (PGP), Panax notoginseng polysaccharides (PNP), and Panax quinquefolius polysaccharides (PQP). First, ATR-FTIR with FD processing was used to establish the discriminant model combined with principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear discriminant analysis (LDA). After that, two-dimensional ATR-FTIR based on single-characteristic temperature as external interference (2D-sATR-FTIR) was established using ATR-FTIR with FD processing. Then, ATR-FTIR with FD processing was combined with PLS to establish and optimize the quantitative regression model. Finally, the established discriminant model and 2D-sATR-FTIR successfully distinguished PGP, PNP and PQP, and the optimal PLS regression model had a good prediction ability for the Panax polysaccharide extracts content. This strategy provides an efficient, economical and nondestructive method for the distinction and quantification of PGP, PNP and PQP in a short detection time.
Panax notoginseng , Spectroscopy, Fourier Transform Infrared/methods , Discriminant Analysis , Least-Squares Analysis , Polysaccharides
Background: Liver metastasis is the major cause of colorectal cancer related death. Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T-cell therapy has been illustrated effective and safe through regional delivery of breast cancer, ovarian cancer and malignant mesothelioma tumors. Herein, we investigated the safety, efficacy, and immune microenvironment of regional delivery of MSLN (CAR) T-cell in the treatment of colorectal carcinoma liver metastases (CRLM). Methods: Second-generation MSLN CAR T-cells were administered by portal vein (PV) or caudal vein (CV, systemic administration) delivery in an orthotopic MSLN+ CRLM nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/γc-/- (NSG) mouse model. A total of 20 mice were randomly divided into control group, non-transduced T cell (NT)-CV group, NT-PV group, MSLN CAR T-cell CV (MSLN-CV) group, and MSLN CAR T-cell PV (MSLN-PV) group, with each group containing four mice to examine the safety and efficacy. The bioluminescence intensity (BLI) of tumor burden, tumor tissue macroscopic and microscopic observation were used to evaluate treatment efficacy. The safety was examined by body weight, survival time, and vital organ damage of mice. CAR T-cell infiltration and cytokine concentration were analyzed by flow cytometry, and immunostaining. The change of immune microenvironment between regional delivery and systemic delivery was investigated on an immune reconstructed CRLM patient-derived xenograft (PDX) model. Additionally, T cell subsets and immunosuppressive markers were examined. Results: PV administration of 1×107/100 µL MSLN CAR T-cells in 20 NSG mice was well tolerated, and no overt toxicity was observed. The tumor burden in the PV group was obviously alleviated. The BLI was (0.73±0.52)×109 in PV group and (1.97±0.11)×109 in CV group (P<0.05), CD8+ granzyme B (GB)+ T cell percentage (MSLN-CV 4.42%±0.47% vs. MSLN-PV 13.5%±4.67%, P<0.01) and cytokine concentration were obviously increased in the MSLN-PV group. In the immune reconstituted CRLM PDX model, intratumor (IT) delivery of MSLN CAR T-cells exhibited much more infiltration of CD4+ and CD8+ T cells accompanied with elevated expression levels of PD-1, LAG-3, and TIM-3. Conclusions: Regional delivery of MSLN-targeted CAR T-cell therapy has encouraging results in the orthotopic CRLM NSG mouse model and PDX model, and converts the tumor microenvironment from cold to hot. This study may provide a new therapeutic approach for CRLM. Further clinical study is needed.
PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Epirubicin , Liver Neoplasms/pathology , Microspheres , Prospective Studies , Treatment Outcome , Chemoembolization, Therapeutic/methods , Doxorubicin , Retrospective Studies
Liquid-liquid phase separation (LLPS) is a reversible process, during which biological macromolecules, including proteins and nucleic acids, condense into liquid membraneless organelles under the influence of weak multivalent interactions. Currently, fluorescence recovery after photobleaching is the primary method used to detect the phase separation of biological macromolecules. Recent studies have revealed the link between abnormal LLPS and the pathogenesis and development of various human cancers. Through phase separation or abnormal phase separation, tumor-related biological macromolecules, such as mRNA, long noncoding RNAs (lncRNAs), and tumor-related proteins, can affect transcriptional translation and DNA damage repair, regulate the autophagy and ferroptosis functions of cells, and thus regulate the development of various tumors. In this review, we summarized the latest research findings on the mechanism of LLPS in the pathogenesis and progression of tumors and elaborated on the promotion or inhibition of autophagy, tumor immunity, DNA damage repair, and cell ferroptosis after abnormal phase separation of biomolecules, including mRNA, lncRNA, and proteins, which subsequently affects the pathogenesis and progression of tumors. According to published findings, many biological macromolecules can regulate transcriptional translation, expression, post-transcriptional modification, cell signal transduction, and other biological processes through phase separation. Therefore, further expansion of the research field of phase separation and in-depth investigation of its molecular mechanisms and regulatory processes hold extensive research potential.
Neoplasms , Phase Separation , Humans , Proteins , RNA, Messenger
The 3',5'-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization-deprotection reaction, resulting in a high yield of 3',5'-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds.
BACKGROUND: Due to the invisibility of the portal vein (PV), how to puncture the PV accurately and safely in transjugular intrahepatic portosystemic shunt (TIPS) creation remains a challenge of the procedure. OBJECTIVES: We aimed to provide the first evaluation of the safety, feasibility, and efficiency of cone beam computed tomography (CBCT)-based three-dimensional (3D) dual-phase vascular image fusion for interventional real-time guided PV puncture during TIPS procedures. MATERIALS AND METHODS: From January 2021 to May 2021, 13 patients undergoing TIPS were prospectively enrolled in this study. Images of the hepatic artery (HA) and PV in 3D were acquired and overlaid on interventional fluoroscopy images in a dual-phase display mode for real-time PV puncture guidance. The number of PV puncture attempts, puncture time, overlaid image accuracy, dose area product, fluoroscopy time, and interventional complications were recorded. RESULTS: Portal vein puncture guided by CBCT-based 3D dual-phase vascular image fusion was successfully performed on 92.3% (12/13) patients. The mean number of PV puncture attempts was 1.8⯱ 0.7 (1-3). The mean puncture time and fluoroscopy time was 3.5⯱ 1.2 (2-6)â¯min and 25.1⯱ 9.4 (15-45)â¯min, respectively. The mean dose area product was 39.49⯱ 7.88 (28.81-52.87)â¯mGym2. The error between the reference position of the fusion image and the interventional PV angiography image was less than 0.5â¯cm. No interventional complication was observed. CONCLUSION: Our results show that 3D dual-phase vascular image fusion might be a safe and feasible technique for interventional real-time guided PV puncture during TIPS. This novel technique might help to reduce the number of PV puncture attempts and the puncture time as well as lower the risks of interventional complications.
OBJECTIVE: This study aimed to assess the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after percutaneous transthoracic lung biopsy (PTLB) guided by C-arm cone-beam computed tomography (CBCT). Furthermore, this study aimed to examine the relationships between PTX and PH with demographics, clinical characteristics, imaging, and PTLB parameters. METHODS: A retrospective analysis was conducted on 192 patients who underwent PTLB at our hospital between January 2019 and October 2022. Incidences of PTX and PH were recorded. PTX was considered clinically significant if treated with chest tube insertion (CTI), and PH if treated with bronchoscopes or endovascular treatments. The various factors on PTX and PH were analyzed using the Chi-squared test and Student t-test. Logistic regression analyses were then used to determine these factors on the correlation to develop PTX and PH. RESULTS: PTX occurred in 67/192 cases (34.9%); CTI was required in 5/67 (7.5%). PH occurred in 63/192 cases (32.8%) and none of these cases required bronchoscopes or endovascular treatments. Lesion diameter (ORPTX = 0.822; ORPH = 0.785), presence of pulmonary emphysema (ORPH = 2.148), the number of samples (ORPH = 1.834), the use of gelfoam (ORPTX = 0.474; ORPH = 0.341) and ablation (ORPTX = 2.351; ORPH = 3.443) showed statistically significant correlation to PTX and PH. CONCLUSIONS: CBCT-guided PTLB is a safe and effective method for performing lung biopsies. The use of gelfoam has been shown to reduce the occurrence of PTX and PH. However, caution should be exercised when combining radiofrequency ablation with PTLB, as it may increase the risk of PTX and PH.
Lung Diseases , Pneumothorax , Humans , Pneumothorax/epidemiology , Pneumothorax/etiology , Pneumothorax/pathology , Incidence , Retrospective Studies , Clinical Relevance , Lung/diagnostic imaging , Lung/pathology , Lung Diseases/diagnostic imaging , Lung Diseases/epidemiology , Lung Diseases/complications , Cone-Beam Computed Tomography , Hemorrhage/epidemiology , Hemorrhage/etiology , Biopsy, Needle/adverse effects , Image-Guided Biopsy/adverse effects , Image-Guided Biopsy/methods , Risk Factors
In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Animals , Rabbits , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/pathology , Nanovaccines , Hypoxia/drug therapy , Tumor Microenvironment
PURPOSE: This study aimed to assess the safety and efficacy of endovascular managements, including splenic vein recanalization (SVR), partial splenic embolization (PSE), and percutaneous transsplenic gastric varices embolization combined with PSE (PSE+GVE), for management of SPH-related variceal hemorrhage (VH). METHODS: A total of 61 patients with SPH-related VH from three hospitals were enrolled and classified into three groups: the SVR group (Group 1, n=24), the PSE+GVE group (Group 2, n=17), and the PSE group (Group 3, n=20). Baseline characteristics and clinical outcomes were compared among the groups. RESULTS: The technical success rates for transhepatic and transsplenic SVR were 27.8% and 34.6%, respectively. No major complications were observed during any of the procedures. The median follow-up period was 53.2 months. The 2-year GI rebleeding rates for Group 1, 2, and 3 were 0%, 5.9%, and 35%, respectively. Groups 1 and 2 have a lower GI rebleeding rate (p = 0.002, p = 0.048, respectively) and better results of the degree of GV (p = 0.003, p = 0.044, respectively) compared to Group 3. No significant differences were found in 2-year GI rebleeding rates and the degree of GV between Group 1 and 2 (p = 0.415, p = 0.352, respectively). CONCLUSION: SVR, PSE+GVE, and PSE seem safe and effective for management of SPH-related VH. SVR appears to be the superior treatment option. Transsplenic access may further increase the SVR success rate. PSE+GVE seems to have comparable outcomes in GV control and GI rebleeding rates compared to SVR, while superior to PSE.
Embolization, Therapeutic , Endovascular Procedures , Esophageal and Gastric Varices , Sinistral Portal Hypertension , Humans , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/diagnostic imaging , Esophageal and Gastric Varices/therapy , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Retrospective Studies , Treatment Outcome , Embolization, Therapeutic/methods , Portal Vein
Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Treatment Outcome , Hepatic Artery/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/therapeutic use , Infusions, Intra-Arterial
In this paper, we established a high power tandem pumped fiber amplifier based on tapered ytterbium-doped fiber (TYDF). The TYDF is developed in-house with a core/inner cladding diameter of 30/250â µm at the small-core region and 48/400â µm at the large-core region. The key parameters of the amplifier in a co-pumped and counter-pumped configuration are experimentally investigated, such as slope efficiency, stimulated Raman scattering (SRS) threshold, and beam quality evolution. Up to 10.28â kW laser free of SRS or transverse mode instability is obtained from the counter-pumped amplifier, and the beam quality factor M2 is 2.29, which is significantly improved compared with the 48/400â µm uniform YDF. To the best of our knowledge, this is the highest average output power achieved so far based on the TYDF. This work could provide a solution for balancing the SRS suppression and high order modes control in high power tandem pumped YDF lasers.
METHODS: HS microspheres were loaded in a solution of hypertonic saline and contrast medium at different ratios. Morphology, size distribution, and drug loading capacity of the microsphere were evaluated. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommended method (dTACE) or a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis, and the microsphere distribution within the tumor were assessed. RESULTS: It was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 µm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11,989.8 ± 5776.6 ng/g) than the concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%. CONCLUSIONS: The size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect.
Aims: To determine the safety and efficacy of microwave ablation (MWA) and transarterial chemoembolization (TACE) with doxorubicin hydrochloride liposome (DHL) in patients with primary liver cancer (PLC) and metastatic liver cancer (MLC). Materials and methods: The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed. Treatment-related adverse events (AEs) were recorded. Local tumor response was evaluated according to the modified RECIST criteria. Local tumor progression-free survival (LTPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Altogether, 96 patients with liver cancer were included (PLC, n â= â45; MLC, n â= â51). Forty (41.7%) patients experienced AEs during treatment, and eight (8.3%) patients developed grade 3 AEs. Compared to before treatment, the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment. The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC. The median OS was not reached in patients with PLC or MLC. The 1-month and 3-month disease control rates reached more than 80% in both groups. Conclusion: MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.
Hepatic ischemia/reperfusion (I/R) injury is an unavoidable complication of liver hepatectomy, transplantation, and systemic shock. Pectolinarigenin (Pec) is a flavonoid with many biological activities, which include anti-inflammatory, anti-apoptotic, and antioxidant stress. This study explored whether Pec pretreatment could reduce hepatic I/R injury and the potential mechanisms at play. After pretreatment of mice and AML12 cells with Pec, I/R and hypoxia/reoxygenation (H/R) models were established. By examining markers related to liver injury, cell viability, oxidative stress, inflammatory response, and apoptosis, the effect of Pec on important processes involved in hepatic I/R injury was assessed. Protein levels associated with the PI3K/AKT/Nrf2 pathway were analyzed by relative quantification to investigate possible pathways through which Pec plays a role in the I/R process. Pec treatment corrected abnormal transaminase levels resulting from I/R injury, improved liver injury, and increased AML12 cell viability. Moreover, Pec treatment inhibited oxidative stress, inflammation and apoptosis and could activate the PI3K/AKT/Nrf2 pathway during I/R and H/R. Further studies found that LY294002 (PI3K inhibitor) suppressed the protective effect of Pec on hepatic I/R injury. In summary, our results show that Pec inhibits oxidative stress, inflammatory responses, and apoptosis, thereby attenuating I/R-induced liver injury and H/R-induced cell damage via activation of the PI3K/AKT/Nrf2 pathway.
Proto-Oncogene Proteins c-akt , Reperfusion Injury , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , NF-E2-Related Factor 2/metabolism , Signal Transduction , Liver/metabolism , Reperfusion Injury/drug therapy , Reperfusion Injury/prevention & control , Reperfusion Injury/etiology , Apoptosis , Oxidative Stress , Ischemia/complications , Ischemia/metabolism
Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."
Purpose: To determine the clinical outcomes of lenvatinib plus PD-1 inhibitor combined with microwave ablation (MWA) and synchronous transarterial chemoembolization (TACE) in patients with progressive hepatocellular carcinoma (pHCC). Materials and Methods: This retrospective study enrolled pHCC patients who underwent lenvatinib plus PD-1 inhibitor combined with MWA and TACE (LP-MT) or lenvatinib combined with MWA and TACE (L-MT) from January 2019 to December 2022. Treatment-related adverse events (AEs) were recorded during the follow-up. Progression-free survival (PFS) and overall survival (OS) were the primary outcomes. The prognostic analyses for survival were performed using Cox proportional hazard regression model. Results: In total, 90 eligible patients with pHCC who received combination therapy were included in the study. Among them, 42 patients received LP-MT and 48 patients received L-MT. There were no significant differences in the baseline characteristics between the two groups. Patients who underwent lenvatinib plus PD-1 inhibitor combined with MWA and TACE had better PFS (median, 10.0 vs 7.4 months, P = 0.03) than those who underwent combination therapy without PD-1 inhibitor, although no significant difference was found in OS (median, 22.5 vs 20.0 months, P = 0.19) between the two groups. The disease control rate of LP-MT group was higher than that of L-MT group (88.1% vs 64.6%, P = 0.01), especially in patients with BCLC stage C (89.3% vs 70.0%, P = 0.03). Univariate and multivariate analyses indicated that treatment method and Child-Pugh class were independent prognostic factors for PFS. The AEs of LP-MT group were comparable and tolerable to those of L-MT group (Any grade, 78.6% vs 62.5%, P = 0.10; Grade 3, 23.8% vs 12.5%, P = 0.16). Conclusion: Lenvatinib plus PD-1 inhibitor may be slightly superior to lenvatinib alone when combined with local interventional therapy for progressive HCC, especially in patients with BCLC stage C.
