Literature review Analysis of the Current State of Targeted Therapy for Gastrointestinal Cancers.

Globally, more than one million new cases of gastric cancer are anticipated by 2024, representing a significant unmet clinical need. It is the fourth most prevalent cancer in men and the seventh most prevalent cancer in women. The pathogens Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) have been linked to a significant number of cases of gastric cancer. On the other hand, the recorded results were not particularly impressive because the gastrointestinal tract (GI) is frequently diagnosed at a very advanced stage, traditional treatments are not very effective, and they have several adverse side effects. In the pursuit of improved systemic therapy, the use of targeted medications has greatly benefited GI care. Immunotherapies, vascular endothelial growth factor, epidermal growth factor receptor, and human epidermal growth factor receptor-2 obstruct the programmed death receptor 1/programmed death-ligand 1 pathway. Advanced gastrointestinal tract (GI) malignancies are increasingly treated at the molecular level. Extended gene RAS and BRAF testing were required to predict the efficacy of trastuzumab (HER2-targeted therapy) and pembrolizumab (anti-PD-1 therapy) for metastatic gastroesophageal (GEJ) malignancies. For metastatic colorectal malignancies, extensive RAS and BRAF testing is required to predict the efficacy of EGFR-targeted therapies. Mismatch repair (MMR) or microsatellite instability (MSI) testing must be performed on all advanced gastrointestinal (GI) malignancies to determine if pembrolizumab or nivolumab with or without ipilimumab will be effective. These advanced tumors are treated with targeted drugs for GI malignancies, and it is now common knowledge that patients must be identified through routine molecular profiling. This article provided a clinical summary of the most recent advances in targeted treatment for GEC and the supporting clinical data, such as their efficacy and safety profiles.

Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study.

BACKGROUND: Furmonertinib (AST2818) is an irreversible, selective, third-generation EGFR tyrosine-kinase inhibitor. We aimed to investigate the efficacy and safety of furmonertinib versus the first-generation EGFR tyrosine-kinase inhibitor gefitinib as first-line treatment in patients with EGFR mutation-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: The FURLONG study is a multicentre, double-blind, randomised, phase 3 study done in 55 hospitals across mainland China. We enrolled patients who were aged 18 years or older and had histologically confirmed, locally advanced or metastatic, stage IIIB, IIIC, or IV unresectable NSCLC with EGFR exon 19 deletions or exon 21 Leu858Arg mutation on tissue biopsy confirmed by a central laboratory. Eligible patients were stratified according to EGFR mutation (exon 19 deletions or exon 21 Leu858Arg) and CNS metastases (with or without) and randomly assigned (1:1) to receive either oral furmonertinib (80 mg/day) or oral gefitinib (250 mg/day) in 21-day cycles until disease progression, the occurrence of intolerable toxicities, withdrawal of consent, or other discontinuation reasons judged by the investigators. Investigators, clinicians, participants, independent review centre (IRC) members, the sponsor, and those analysing the data were all masked to treatment allocation. The primary endpoint was IRC-assessed progression-free survival and, along with safety, was analysed in the full analysis set, which comprised all randomly assigned patients who had received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03787992, and is ongoing for survival follow-up. FINDINGS: Between May 30, 2019, and Dec 5, 2019, 750 patients were screened, of whom 358 were randomly assigned to receive either furmonertinib and gefitinib-matching placebo (n=178) or gefitinib and furmonertinib-matching placebo (n=180). 178 patients randomly assigned to furmonertinib and 179 patients randomly assigned to gefitinib were treated and were included in the full analysis set. Median follow-up was 21·0 months (IQR 18·0-23·5) in the furmonertinib group and 21·0 months (18·0-23·5) in the gefitinib group. Median IRC-assessed progression-free survival was 20·8 months (95% CI 17·8-23·5) in the furmonertinib group and 11·1 months (9·7-12·5) in the gefitinib group (hazard ratio 0·44, 95% CI 0·34-0·58; p<0·0001). Treatment-related adverse events of a grade 3 or more occurred in 20 (11%) of 178 patients in the furmonertinib group and in 32 (18%) of 179 patients in the gefitinib group. Treatment-related serious adverse events were reported in ten (6%) patients in the furmonertinib group and in 11 (6%) patients in the gefitinib group. Ten (6%) patients in the furmonertinib group and three (2%) patients in the gefitinib group died due to adverse events, which were all judged to be possibly unrelated to study treatment by the investigators. INTERPRETATION: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive NSCLC, along with an acceptable safety profile without new signals. Furmonertinib is a new potential treatment option for this population. FUNDING: Shanghai Allist Pharmaceuticals and the China National Major Project for New Drug Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Phototherapy Facilitates Tumor Recruitment and Activation of Natural Killer T cells for Potent Cancer Immunotherapy.

Adoptively transferred natural killer T (NKT) cells confer distinct cancer surveillance without causing obvious side effects, making them a promising candidate for cancer immunotherapy. However, their therapeutic efficacy is limited by inefficient tumor infiltration and inadequate activation in an immunosuppressive tumor microenvironment. To overcome these obstacles, we develop a strategy of using photothermal therapy (PTT) to promote the antitumor ability of adoptively transferred NKT cells. The transferred NKT cells are efficiently recruited to PTT-treated tumors in response to PTT-created inflammation. Moreover, PTT treatment promotes the activation of NKT cells and enhances the NKT cell-initiated immune cascade. As a consequence, the combined therapy of PTT plus NKT cell transfer exhibits excellent growth inhibition of local tumors. Moreover, it efficiently rejects distant tumors and elicits long-term immunological memory to prevent tumor recurrence. Overall, the current study opens new paths to the clinical translation of NKT cells for cancer immunotherapy.

Iodine nutrition status of women after 10 years of Lipiodol supplementation: a cross-sectional study in Xinjiang, China.

This study examined the contribution of long-term use of Lipiodol capsules, as a supplement to iodised salt to the control of iodine deficiency disorders among women in Xinjiang of China. A total of 1220 women across Kashgar, Aksu, Turpan and Yili Prefectures were surveyed in 2017. Lipiodol capsules were administered twice yearly in Kashgar and once yearly in Aksu and Turpan, but not in Yili. Urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody, thyroid peroxidase antibody and thyroid volume values were assessed. All the women in the four areas were in a state of non-iodine deficiency by UIC. The UIC were higher than adequate in Kashgar and Aksu (619·4 v. 278·6 µg/l). Thyroid hormone levels differed significantly in Turpan and Yili (FT3: 4·4 v. 4·6 pmol/l, FT4: 13·8 v. 14·2 pmol/l, TSH: 2·0 v. 2·7 mIU/l), but did not differ significantly in Kashgar, Aksu and Yili. The four areas did not differ significantly with regard to thyroid nodules, autoimmune thyroiditis or goitre. However, the detection rates of subclinical hypothyroidism (16·6 %) and total thyroid dysfunction (25·4 %) were higher among women in Yili. The supplementation with Lipiodol capsules had improved the iodine nutrition status of women in iodine-deficient areas of Xinjiang since 2006. To avoid negative effects of excess iodine, we suggest a gradual discontinuation of Lipiodol capsules in women with special needs based on the existing iodine nutrition level of local women.

ß-Elemene enhances radiosensitivity in non-small-cell lung cancer by inhibiting epithelial-mesenchymal transition and cancer stem cell traits via Prx-1/NF-kB/iNOS signaling pathway.

Radiation therapy is widely used to treat a variety of malignant tumors, including non-small-cell lung cancer (NSCLC). However, ionizing radiation (IR) paradoxically promotes radioresistance, metastasis and recurrence by inducing epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). Here, we developed two NSCLC radioresistant (RR) cell lines (A549-RR and H1299-RR) and characterized their motility, cell cycle distribution, DNA damage, and CSC production using migration/invasion assays, flow cytometry, comet assays, and sphere formation, respectively. We also evaluated their tumorigenicity in vivo using a mouse xenograft model. We found that invasion and spheroid formation by A549-RR and H1299-RR cells were increased as compared to their parental cells. Furthermore, as compared to radiation alone, the combination of ß-elemene administration with radiation increased the radiosensitivity of A549 cells and reduced expression of EMT/CSC markers while inhibiting the Prx-1/NF-kB /iNOS signaling pathway. Our findings suggest that NSCLC radioresistance is associated with EMT, enhanced CSC phenotypes, and activation of the Prx-1/NF-kB/iNOS signaling pathway. They also suggest that combining ß-elemene with radiation may be an effective means of overcoming radioresistance in NSCLC.

Arginine hypomethylation-mediated proteasomal degradation of histone H4-an early biomarker of cellular senescence.

Senescence is accompanied with histones level alteration; however, the roles and the mechanisms of histone reduction in cellular senescence are largely unknown. Protein arginine methyltransferase 1 (PRMT1) is the major enzyme that generates monomethyl and asymmetrical dimethyl arginine. Here we showed that abrogation of PRMT1-mediated senescence was accompanied with decreasing histone H4 level. Consistently, under multiple classic senescence models, H4 decreasing was also been found prior to the other 3 core histones. Noticeably, asymmetric demethylation of histone H4 at arginine 3 (H4R3me2as), catalyzed by PRMT1, was decreased prior to histone H4. In addition, we showed that the PRMT1-mediated H4R3me2as maintained H4 stability. Reduction of H4R3me2as level increased the interaction between proteasome activator PA200 and histone H4, which catalyzes the poly-ubiquitin-independent degradation of H4. Moreover, H4 degradation promoted nucleosome decomposition, resulting in increased senescence-associated genes transcription. Significantly, H4 was restored by 3 well-informed anti-aging drugs (metformin, rapamycin, and resveratrol) much earlier than other senescence markers detected under H2O2-induced senescence. Thus, we uncovered a novel function of H4R3me2as in modulation of cellular senescence via regulating H4 stability. This finding also points to the value of histone H4 as a senescence indicator and a potential anti-aging drug screening marker.

Isolation, identification, and characterization of diesel-oil-degrading bacterial strains indigenous to Changqing oil field, China.

In the present study, 12 indigenous diesel-oil-degrading bacteria were isolated from the petroleum-contaminated soils of the Changqing oil field (Xi'an, China). Measurement of the diesel-oil degradation rates of these strains by the gravimetric method revealed that they ranged from 42% to 66% within 2 weeks. The highest degradation rates were observed from strains CQ8-1 (66%), CQ8-2 (62.6%), and CQ11 (59%), which were identified as Bacillus thuringiensis, Ochrobactrum anthropi, and Bordetella bronchialis, respectively, based on their 16S rDNA sequences. Moreover, the physiological and biochemical properties of these three strains were analyzed by Gram staining, catalase, oxidase, and Voges-Proskauer tests. Transmission electron microscopy showed that all three strains were rod shaped with flagella. Gas chromatography and mass spectrometric analyses indicated that medium- and long-chain n-alkanes in diesel oil (C11-C29) were degraded to different degrees by B. thuringiensis, O. anthropi, and B. bronchialis, and the degradation rates gradually decreased as the carbon numbers increased. Overall, the results of this study indicate strains CQ8-1, CQ8-2, and CQ11 might be useful for environmentally friendly and cost-effective bioremediation of oil-contaminated soils.

Preparation and Evaluation of Mosapride Citrate Dual-Release Dry Suspension.

In this paper, a novel formulation of dual-release dry suspension of mosapride citrate (DRDS-MC) was designed which can be quickly released in the stomach while having sustained-release effect. Co-grinding mixture of mosapride citrate (MC) together with L-HPC as hydrophilic excipient was prepared in order to improve the solubility of MC. The co-grinding mixture was characterized by solubility studies, DSC, X-RD, SEM, FTIR, and size distribution before the preparation of the DRDS-MC. Then, the co-grinding mixture was used to prepare DRDS-MC via wet granulation method. The evaluation of DRDS-MC was focused on physicochemical properties, intestinal absorption, and pharmacokinetics. The results of DSC, X-RD, SEM, FTIR, and size distribution indicated that MC resides in co-grinding mixture with no crystalline changes, hydrogen bonds made L-HPC greatly improving the solubility of MC. Then, the dissolution of DRDS-MC reached 70% in pH 1.2 within 2 h, and the 12-h dissolution of MC in pH 6.8 was nearly 80%. The sedimentation volume after 3 h was 0.94 and redispersibility was good. The linear regression equation between in vitro release of DRDS-MC and intestinal absorption fraction in rats was: Y = 29.215 + 47.535*X (r = 0.952). At last, pharmacokinetic studies in beagle dogs demonstrated that DRDS-MC has prolonged effect compared with commercial formulation Gasmotin as a reference. All results indicated that the DRDS-MC could be quickly released in the stomach while having sustained-release effect.

A switchable NO-releasing nanomedicine for enhanced cancer therapy and inhibition of metastasis.

Clinical chemotherapy for cancer is limited by the physiological barrier of tumors, resulting in low drug delivery to tumors, poor efficacy of drugs and inability to block tumor metastasis. Here we developed an intelligent switchable nitric oxide (NO)-releasing nanoparticle, IPH-NO, which loads a photosensitizer (IR780) and the chemotherapy drug paclitaxel (PTX) into NO donor-S-nitrosated human serum albumin (HSA-NO). NO exhibits two effects based on its concentration: enhancement of chemotherapy by increasing the enhanced permeability and retention (EPR) effect at low concentrations and direct killing of cancer cells at high concentrations. IPH-NO can slowly release NO in the presence of glutathione to boost tumor vascular permeability and improve drug accumulation. Near-infrared light irradiation was utilized to induce a quick release of NO that can directly kill cancer cells at high concentrations. This combination of phototherapy and NO gas therapy activated by NIR together with chemotherapy showed significant effects in tumor inhibition. Furthermore, IPH-NO blocked tumor metastasis by inhibiting epithelial mesenchymal transition. PH-NO provides a novel strategy to control NO release at tumor site for drug accumulation and combination therapies, consequently potentiating the anticancer efficacy and inhibiting tumor metastasis.

Biosynthesis of selenium nanoparticles, characterization and X-ray induced radiotherapy for the treatment of lung cancer with interstitial lung disease.

Selinium nanoparticles (SeNPs) with minimal toxicity and efficient antioxidant properties were reported earlier for their anti-carcinogenic influence against various types of cancers, thus elevating its potential. In the present study, the anti-carcinogenic effect of selenium nanoparticles against lung cancer was studied. Selenium nanoparticles were biosynthesized and were characterized using UV- Vis absorption spectroscopy. A decrease in the absorption intensity was recorded with the increase in time, which represented the protein consumption during the reduction of SeO32- to Se0. The calculated average crystalline size from XRD studies of the synthesized selenium nanoparticles was found to be 88.89 nm which was in accordance with the TEM analysis while the SAED pattern has disclosed hexagonal ring structure with diffraction ring pattern.MTT assay was performed to evaluate the radio-sensitizing effect of selenium nanoparticles under the X-ray influence against cancer as well as healthy cell lines. SeNPs showed potent cytotoxicity effect in cancer cells whereas it showed relatively less toxic effect in normal healthy cells. However, caspase-3 activity was even more elevated when subjected to X-ray exposure than in the absence. These findings apparently revealed the cytotoxic potential of SeNPs + X-ray combination in the lung cancer cell lines.

Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness.

Cisplatin is a first line chemotherapy in lung cancer, but decreased susceptibility may limit its application. In solid tumors, hypoxia alters the microenvironment and is associated with proliferation, metastasis, and drug sensitivity. The hypoxia-induced desensitization of cisplatin is not clearly elucidated. 20 (R)-Ginsenoside (Rg3), the traditional Chinese medicine, is extracted from ginseng and has antitumor activities. In this study, we evaluated if Rg3 is effective in improving cisplatin sensitivity by blocking hypoxia. We found that the inhibition of proliferation potential by cisplatin was reduced in cobalt chloride (CoCl2)-induced hypoxia in lung cancer cells. Hypoxia caused alterations in epithelial-mesenchymal transition (EMT), which were detected by cellular morphology and EMT protein markers, and in stemness analyzed by spheroid formation and marker molecules. Hypoxia also activated EMT, which was mediated by the nuclear factor κB (NF-κB) pathway, and stemness, and Rg3 inhibited the activation of the NF-κB pathway. Furthermore, Rg3 could increase the sensitivity to cisplatin by inhibiting EMT and stemness in hypoxic lung cancer cells, and this effect was confirmed in vivo. In conclusion, Rg3 may improve the sensitivity of cisplatin in lung cancer therapy.

Ginsenoside Rg3 induces FUT4-mediated apoptosis in H. pylori CagA-treated gastric cancer cells by regulating SP1 and HSF1 expressions.

Helicobacter pylori (H. pylori) cytotoxin associated antigen A (CagA) plays a significant role in the development of gastric cancer. Ginsenoside Rg3 is a herbal medicine which inhibits cell proliferation and induces apoptosis in various cancer cells. Fucosylation plays important roles in cancer biology as increased fucosylation levels of glycoproteins and glycolipids have been reported in many cancers. Fucosyltransferase IV (FUT4) is an essential enzyme, catalyzes the synthesis of LewisY oligosaccharides and is regulated by specificity protein 1 (SP1) and heat shock factor protein 1 (HSF1) transcription factors. Herein, we studied the mechanism action of Rg3 apoptosis induction in gastric cancer cells. We treated the gastric cancer cells with CagA followed by Rg3, and analyzed their ability to induce apoptosis by evaluating the role of FUT4 as well as SP1 and HSF1 expressions by Western blot, flow cytometry and ELISA. We found that Rg3 significantly induced apoptosis in CagA treated gastric cancer cells, as evidenced by nuclear staining of 4-6-diamidino-2-phenylindole (DAPI) and Annexin-V/PI double-labeling. In addition, Rg3 significantly increased the expression of pro-apoptotic proteins and triggered the activation of caspase-3, -8, and -9 and PARP. Moreover, Rg3-induced apoptotic mechanisms indicated that Rg3 inhibited FUT4 expression through SP1 upregulation and HSF1 downregulation. Hence, Rg3 therapy is an effective strategy for gastric cancer treatment. Furthermore SP1 and HSF1 may serve as potential diagnostic and therapeutic targets for gastric cancer.

Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.

The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 µg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer.

Clinical observation of liver cancer patients treated with axitinib and cabozantinib after failed sorafenib treatment: a case report and literature review.

Hepatocellular carcinoma (HCC) is a major pathological type of primary liver cancer. Sorafenib has demonstrated definite efficacy in targeted therapy for HCC. However, when treatment with sorafenib fails, suitable drugs must be found for further treatment. This article reports a case of an HCC patient who was treated with angiogenesis inhibitor axitinib and c-Met inhibitor cabozantinib following treatment with sorafenib. The report focuses on clinical treatment and toxicity. Rational application of targeted therapy is also explored.

[Effect of pungent dispersion bitter purgation method on the esophageal mucosal intercellular space of reflux esophagitis model rats].

OBJECTIVE: To observe the effect of pungent dispersion bitter purgation method (PDBPM) on the esophageal mucosal intercellular space of reflux esophagitis (RE) model rats. METHODS: Totally 100 Wistar rats were randomly divided into the control group, the model group, the Western medicine group (WM), the Chinese medicine group (CM), 25 rats in each group. Rats in the control group only received switch operation. Rats in the rest three groups received modified partial cardia muscle incision combined pylorus ligation of external parts to prepare the RE rat model. Starting from the 3rd day after operation, WM mixture (Motilium 3. 2 mg/kg + Omeprazole Capsule 4.3 mg/kg + Hydrotalcite Tablet 161.4 mg/kg) was administered by gastrogavage to rats in the WM group. Rats in the CM group was administered by gastrogavage with Modified Banxia Xiexin Decoction (5.7 g/kg), 2.5 mL each time, twice daily for 14 consecutive days. Equal volume of normal saline was administered by gastrogavage to rats in the control group and the model group. On day 7 and 14, the lower esophagus pH value, general specimen of mucosa and histopathologic changes were observed. Intercellular spaces of esophageal epithelium were measured for a control study. RESULTS: Compared with the same group at day 7, the lower esophagus pH value increased at day 14 (P < 0.01); the naked eye integral of esophageal mucosa and intercellular spaces of esophageal epithelium also decreased at day 14 in the CM group and the WM group (P < 0.05). Compared with the control group at the same time point, the lower esophagus pH value decreased in the model group (P < 0.01). The naked eye integral of esophageal mucosa, and intercellular spaces of esophageal epithelium increased in the model group with increased intercellular spaces (P < 0.01). Compared with the model group at the same time point, the lower esophagus pH value increased and the naked eye integral of esophageal mucosa decreased in the CM group and the WM group at day 7 and 14 (P < 0.01). Intercellular spaces of esophageal epithelium of RE model rats at day 14 was lower in the CM group and the WM group than in the model group (P < 0.01). Compared with the WM group, the lower esophagus pH value decreased at day 7 in the CM group (P < 0.05); the naked eye integral of esophageal mucosa and intercellular spaces of esophageal epithelium decreased at day 14 in the CM group (P < 0.05). CONCLUSIONS: PDBPM had favorable treatment effect on RE model rats. The therapeutic effect was more obvious along with the therapeutic course went by. Its mechanism might be achieved through good repair effect on damaged mucosa, increasing the pressure of esophageal sphincter, and inhibiting gastric acid.

A novel magnetic nanoparticle hyperthermia combined with ACMF-dependant drug release by DAMMs injection in VX-2 liver tumors.

In this paper, we investigated the feasibility and effect of a novel combination therapy of magnetic nanoparticles (MNPs) hyperthermia with anticancer drugs for solid malignancies using doxorubicin-loaded alginate-templated magnetic microcapsules (DAMMs) in an animal liver cancer model. Firstly, DAMMs containing 18 nm gamma-Fe2O3 with doxorubicin (Dox) were synthesized and characterized. Then, the particular behavior of Dox release under external alternating current magnetic filed (ACMF) was tested in vitro. Moreover, to obtain accurate thermotherapy, the dose of DAMMs and temperature rise were computed by Hyperthermia treatment plan (HTP) and a fiber optic temperature sensor (FOTS) was used to monitor the temperature rise during treatments on VX-2 liver tumor-bearing rabbits. Furthermore, the therapeutic effect was studied by histopathological examinations and animal survival. The results showed that ACMF can induce Dox fast release during the treatment and the high MNPs content of DMMAs guaranteed the temperature rise for hyperthermia in tumors. The rabbits bearing VX-2 tumors in the magnetic hyperthermia using DMMAs group gained the most tumor necrosis and survival time. It was indicated that DAMMs-based magnetic hyperthermia could be a feasible and effective remedy which could be targeted at liver tumors by dual effects of hyperthermia and chemotherapy.

Synthesis of magnetic/luminescent alginate-templated composite microparticles with temperature-dependent photoluminescence under high-frequency magnetic field.

Highly magnetic luminescent alginate-templated composite microparticles were successfully synthesized by a novel process combining emulsification and layer-by-layer self-assembly techniques. The composite microparticles were characterized by ζ-potential analyzer, transmission electron microscope, X-ray diffraction, Fourier transform infrared spectroscope, fluorescence spectrophotometer, and vibrating sample magnetometer. Experimental observations indicated that the composite microparticles had excellent magnetic properties, and its photoluminescence could be precisely controlled by varying the number of deposition cycles of polyelectrolytes and CdTe/polyelectrolyte multilayers. Moreover, the composite microparticles could be heated up in a high-frequency magnetic field and demonstrated linear temperature-dependent photoluminescence over the range from room temperature to hyperthermia temperature. The composite microparticles are expected to be promising candidates for biomedical applications, such as immunoassay, biosensing and imaging, and cancer diagnosis and treatment.

Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.

BACKGROUND: Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma. METHODS: Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00492752. FINDINGS: 271 patients from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6.5 months (95% CI 5.56-7.56) in patients treated with sorafenib, compared with 4.2 months (3.75-5.46) in those who received placebo (hazard ratio [HR] 0.68 [95% CI 0.50-0.93]; p=0.014). Median TTP was 2.8 months (2.63-3.58) in the sorafenib group compared with 1.4 months (1.35-1.55) in the placebo group (HR 0.57 [0.42-0.79]; p=0.0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10.7%]), diarrhoea (nine patients [6.0%]), and fatigue (five patients [3.4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11.4%]) and diarrhoea (11 patients [7.4%]); these adverse events rarely led to discontinuation. INTERPRETATION: Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma.

A novel mannose-binding tuber lectin from Typhonium divaricatum (L.) Decne (family Araceae) with antiviral activity against HSV-II and anti-proliferative effect on human cancer cell lines.

A novel mannose-binding tuber lectin with in vitro antiproliferative activity towards human cancer cell lines and antiviral activity against HSV-II was isolated from fresh tubers of a traditional Chinese medicinal herb, Typhonium divaricatum (L.) Decne by a combined procedure involving extraction, ammonium sulfate precipitation, ion exchange chromatography on DEAE-SEPHAROSE, CM-SEPHAROSE and gel-filtration on sephacryl S-200. The apparent molecular mass of the purified Typhonium divaricatum lectin (TDL) was 48 kDa. TDL exhibits hemagglutinating activity toward rabbit erythrocytes at 0.95 microg/ml, and its activity could be strongly inhibited by mannan, ovomucoid, asialofetuin and thyroglobulin. TDL showed antiproliferative activity towards some well established human cancer cell lines, e.g. Pro-01 (56.7 +/- 6.8), Bre-04 (41.5 +/- 4.8), and Lu-04 (11.4 +/- 0.3). The anti-HSV-II activity of TDL was elucidated by testing its HSV-II infection inhibitory activity in Vero cells with TC(50) and EC(50) of 5.176 mg/ml and 3.054 microg/ml respectively. The full-length cDNA sequence of TDL was 1145 bp and contained an 813-bp open reading frame (ORF) encoding a 271 amino acid precursor of 29-kDa. Homology analysis showed that TDL had high homology with many other mannose-binding lectins. Secondary and three-dimensional structures analyses showed that TDL is heterotetramer and similar with lectins from mannose-binding lectin superfamily, especially those from family Araceae.

[Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus].

BACKGROUND & OBJECTIVE: H101 is an E1B-55 kDa gene-deleted replication-selective adenovirus, which showed a significant antitumor activity. This study was to compare effects and toxicities of intratumoral H101 injection combined with cisplatin plus 5-fluorouracil (PF) regimen or adriamycin plus 5-fluorouracil (AF) regimen versus PF or AF regimen alone in treating patients with head and neck or esophagus squamous cell cancer. METHODS: A total of 160 patients were recruited. PF regimen (cisplatin 20 mg/m(2) ivgtt, qd x 5d; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients have no history of PF chemotherapy,or sensitive to PF chemotherapy,while AF regimen (adriamycin 50 mg/m(2) iv,d1; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients didn't response to PF regimen. All patients were randomized to either receive intratumoral H101 injection (5.0 x 10(11)-1.5 x 10(12) VP/day for 5 consecutive days every 3 weeks) or not. Treatment repeated every 3 weeks,all patients have to receive at least 2 cycles of chemotherapy. RESULTS: Among 123 accordant patients,overall response rate of PF plus H101 group (group A1) was 78.8% (41/52),of PF alone group (group B1) was 39.6% (21/53),of AF plus H101 group (group A2) was 50.0% (7/14),of AF alone group (group B2) was 50.0% (2/4). Differences of response rates between group A1 and group B1,between group A1+A2 and group B1+B2 were significant (P=0.000). Main side effects were fever (45.7%), injection site reaction (28.3%),and influenza-like symptoms (9.8%). CONCLUSION: Intratumoral H101 injection showed a distinct efficacy in patients with squamous cell cancer of head and neck or esophagus,and was relatively safe.