Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Sorafenib-Loaded Cu2-xSe Nanoparticles Boost Photothermal-Synergistic Targeted Therapy against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2-xSe@SOR@PEG (CSP), that is based on a photothermal Cu2-xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.

Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.

Sorafenib-Conjugated Zinc Phthalocyanine Based Nanocapsule for Trimodal Therapy in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model.

Sorafenib, a multitargeted kinase inhibitor, has been reported to elicit a limited therapeutic effect in hepatocellular carcinoma (HCC). Currently, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful modality for cancer therapy. However, few studies have been reported the effectiveness of the combination of sorafenib with PDT and PTT in HCC. Herein, we designed and synthesized bovine serum albumin (BSA)-coated zinc phthalocyanine (ZnPc) and sorafenib (SFB) nanoparticle (ZnPc/SFB@BSA). The obtained ZnPc/SFB@BSA was able to trigger PDT, PTT, and chemotherapy. After irradiation by a 730 nm light, ZnPc/SFB@BSA significantly suppressed HCC cell proliferation and metastasis while promoted cell apoptosis in vitro. Furthermore, intravenous injection of ZnPc/SFB@BSA led to dramatically reduced tumor growth in an orthotopic xenograft HCC model. More importantly, ZnPc/SFB@BSA presented low toxicity and adequate blood compatibility. Therefore, a combination of ZnPc with sorafenib via BSA-assembled nanoparticle can markedly suppress HCC growth, representing a promising strategy for HCC patients.

Early diagnosis and therapeutic choice of Klebsiella pneumoniae liver abscess.

Nowadays, pyogenic liver abscess (PLA) is still a common and severe intra-abdominal infection, and Klebsiella pneumoniae had emerged as the most common pathogenic bacteria worldwide in the past ten years. Our study aims to achieve an early pathogenic diagnosis and rational therapy modality for Klebsiella pneumoniae liver abscess (KLA) through clinical data analysis. A total of 197 inpatients in Zhongshan Hospital, Shanghai, diagnosed as having liver abscess between March 2001 and September 2009 were enrolled. Patients with monomicrobial infection were divided into two groups: patients with K. pneumoniae liver abscess (KLA group, n=106) and those with non-Klebsiella pneumoniae liver abscess (NKLA group, n=56). A retrospective analysis was made between these two groups on the aspects of underlying diseases, clinical characteristics, laboratory data, culture results, and imaging findings. To evaluate the effects of different medical interventions, monomicrobial KLA patients were further divided into four subgroups (percutaneous liver aspiration, aspiration plus antibiotics flushing, aspiration plus retained catheter, and aspiration plus antibiotics flushing and retained catheter), and corresponding therapeutic effects were analyzed. KLA was more likely to occur in patients with coexisting diseases such as diabetes mellitus (53.77% vs 25.00%, P=0.001) and hepatic adipose infiltration (16.04% vs 5.36%, P=0.029). Compared to NKLA group, clinical characteristics including abdominal pain (40.57% vs 57.14%, P=0.044), hypodynamia (19.81% vs 46.43%, P=0.001), and hepatomegaly (4.72% vs 14.29%, P=0.033) were much milder, but with a higher fasting blood glucose level (7.84±0.36 vs 5.76±0.30, P=0.001) on admission in KLA group. In addition, KLA abscess often appeared singly in the right lobe of the liver with gas forming nature (32.88% vs 13.51%, P=0.039), unsmooth rim (71.23% vs 40.54%, P=0.002), and dynamic septum enhancement (41.10% vs 16.22%, P=0.009). Compared to mono aspiration subgroup, additional antibiotic flushing could not further improve clinical outcomes of KLA patients (P>0.05); however, the retained catheter showed obvious advantage in reducing abscess diameter (34.38±3.25 mm vs 22.67±2.37 mm, P=0.017). It can be concluded that the strong association with diabetes, milder clinical symptoms, and gas-forming nature in CT images makes early pathogenic diagnosis of KLA possible. Comparatively, ultrasonography-guided percutaneous liver aspiration with retained catheter may be the most rational intervention modality of KLA.

[Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer].

OBJECTIVE: To investigate the effect of magnetic doxorubicin liposome (MDL) in the targeting treatment of nude mice bearing colon cancer. METHODS: Human colon cancer line LoVo cells were implanted hypodermically into nude mouse. Two weeks after the mouse was killed and the tumor was taken out and cut into small pieces to be retransplanted into nude mice so as to establish an experimental model. MDL was prepared by reverse-phase evaporation method. The particle size and structure of MDL were evaluated. Eighteen nude mice with colon cancer were divided into 3 groups of 3 mice: free DOX group, MDL (-) group (no magnetic field was added to the tumor surface), and MDL (+) group (magnetic field with the strength of 4,500 G was added). DOX of the dosage of 5 mg/kg was injected through the caudal vein in these 3 groups. Then the mice were killed 30 minutes after. Fluorescence spectrophotometry was used to examine the concentrations of DOX in the tissues and plasma. Another 36 nude mice with colon cancer were divided into 6 groups of 6 mice: normal saline group (as controls), DOX group, blank liposome group, magnetic liposome group, MDL (-) group (non-magnetic alloy was implanted into the tumor), and MDL (+) group (rare earth magnet was implanted into the tumor). The body weight, longest diameter of tumor, and short diameter vertical to the longest diameter were calculated regularly. The mice were killed 11 days after. The tumors were taken out to undergo staining and light microscopy. Flow cytometry was used to examine the apoptosis of tumor cells. RESULTS: The particle size of MDL was 230 nm and the magnetic particles (Fe(3)O(4)) were evenly distributed within the liposome. The DOX concentration in tumor tissue of the MDL (+) group was remarkably higher than those of the DOX and MDL (-) groups (both P < 0.05). The DOX concentration in heart and kidney of the DOX group were higher than those of the other 2 groups, and the plasma DOX concentrations of the DOX group was significantly lower than those of the other groups (all P < 0.05). The growth speed of tumor in the MDL (+) group was significantly lower, and the tumor weight was significantly less than in other groups. CONCLUSION: Magnetic doxorubicin liposome, as a carrier of anticancer drug, has a good targeting function toward the magnetite and has a significant anticancer effect.