[Value of serum levels in predicting lower extremity deep vein thrombosis after hip joint surgery in the elderly].

OBJECTIVE: To explore the value of serum D-dimer (D-D), fibrinogen (FIB), platelet (PLT), C-reactive protein (CRP) and tissue plasminogen activator inhibitor (PAI)-1 levels in predicting lower extremity deep vein thrombosis (DVT) after hip joint surgery in the elderly. METHODS: A retrospective analysis was performed on 165 elderly patients with hip joint surgery admitted from February 2020 to May 2022, including 89 males and 76 females, aged from 60 to 75 years old with an average of (66.43±5.48) years, and there were 102 cases of femoral neck fracture and 63 cases of femoral head necrosis. Serum levels of D-D, FIB, PLT, CRP and PAI-1 tests were performed in all patients within 24 hours after admission, and the patients were divided into DVT group and non-DVT group according to whether they developed DVT. RESULTS: The levels of D-D, FIB, PLT, CRP, and PAI-1 in the DVT group were higher than those in the non-DVT group (P<0.001). Spearman analysis showed that DVT was positively correlated with PLT, CRP, D-D, FIB, and PAI-1 levels (r=0.382, 0.213, 0.410, 0.310, 0.353, all P<0.001). The results of binary Logistic regression analysis showed that D-D and PLT were independent factors affecting the occurrence of DVT (OR=0.038, 0.960, P=0.032, 0.011). The area under curve (AUC) of D-D, FIB, PLT, CRP, PAI-1, and the five combined predictions for DVT were 0.843, 0.692, 0.871, 0.780, 0.819, and 0.960, respectively. The AUC of the five combined predictions was higher than that of the single prediction (P<0.05). CONCLUSION: D-D, FIB, PLT, CRP and PAI-1 are effective in predicting DVT after hip surgery in the elderly, and the combined prediction of the five factors has higher efficacy.

A novel fluoropolymer as a protein delivery vector with robust adjuvant effect for cancer immunotherapy.

The inefficient treatment using protein-based nanovaccines is largely attributed to their inadequate immunogenicity. Herein, we developed a novel fluoropolymer (PF) via ring-opening polymerization and constructed a fluoropolymer-based nanovaccine for tumor immunotherapy. Due to the existence of fluoroalkyl chains, PF not only played a crucial role in tumor antigen delivery but also exhibited a remarkable adjuvant effect in enhancing the immunogenicity of nanovaccines. The nanovaccines formed by mixing PF with a model antigen ovalbumin (OVA) enhanced the uptake of antigen proteins by dendritic cells (DCs) and promoted the maturation and antigen presentation of DCs. Compared with free OVA, PF/OVA showed better efficacy in both pre-cancer prevention and tumor treatment. Furthermore, the proportion of CD4+ T and CD8+ T cells was significantly increased in lymph nodes and tumors of mice immunized with PF/OVA. Additionally, there was a great enhancement in the levels of key anti-tumor cytokines (TNF-α and IFN-γ) in the serum of the PF/OVA immunized mice. Our research has shown that fluoropolymer PF applied as a protein vector and adjuvant has great potential for the development of nanovaccines with robust immunogenicity.

Sesquiterpenoids and their quaternary ammonium hybrids from the mycelium of mushroom Stereum hirsutum by medium optimization.

The fungal genus Stereum (Stereaceae) produces a broad variety of specialised metabolites, including a wide range of terpenes. This probably relates to the presence of an extensive biosynthetic machinery for this group of compounds: genomic analysis of Stereum hirsutum has identified 16 terpene synthase gene clusters, 6 polyketide synthase gene clusters, and 1 polyketide synthase non-ribosomal polypeptide heterodimer gene cluster in S. hirsutum FP-91666. In the present study, the One Strain Many Compounds (OSMAC) approach was employed to discover undescribed metabolites from this strain. Fermentation was carried out in five media and the products of the strain cultivated on different media were analyzed by LC-MS. From cultures grow in WGB medium (30.0 g wheat bran, 20.0 g glucose, 1.5 g KH2PO4, and 1.5 g MgSO4), four previously undescribed metabolites, a sesquiterpene sterostrein X and three mixed terpenes (stereumamides I-K) were isolated, together with seven known compounds (drimene-2,11-diol, stereumamide E, stereumamide D, stereumamide B, stereumamide A, stereumamide C, and sterostrein Q). The drimane-type sesquiterpene drimene-2,11-diol was found in S. hirsutum FP-91666 for the first time. All structures were elucidated by spectroscopic data analysis. The absolute configurations of stereumamides I, J and K were assigned by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. An anti-Mycobacterium tuberculosis experiment showed that stereumamides I-K and sterostrein Q had weak antibacterial activity against this pathogen.

Secondary Metabolites and Their Bioactivities Produced by Paecilomyces.

Paecilomyces, a common saprobic filamentous fungus, not only plays an important role in biological control, but also has applications in medicine, food, and environmental protection. In this paper, 223 secondary metabolites and their bioactivities from 13 known species and various unidentified strains of Paecilomyces are reviewed. Their structures can be described as polyketide, terpenoid, peptide, alkaloid, quinone, pyrone, sterol, and fatty acid. They have been demonstrated varying biological activities, including antimicrobial, antitumor, insecticidal, antiplasmodial, antimalarial, nematicidal, herbicidal, and enzyme-inhibiting. This review provides a comprehensive overview of secondary metabolites and their biological activities from strains of Paecilomyces.

Antibacterial diketopiperazines from an endophytic fungus Bionectria sp. Y1085.

Two new diketopiperazines (1, 2), one new polyprenol (3), together with 19 known compounds (4-22) were obtained from the EtOAc extract of Bionectria sp. Y1085, an endophytic fungus isolated from the plant Huperzia serrata. Their structures were elucidated by extensive NMR and MS analysis. Bionectin D (1) is a rare diketopiperazine with a single methylthio substitution at the α-carbon of cyclized amino acid residue. The antibacterial activity of compounds was assayed against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium ATCC 6539, and some metabolites (1, 2, 10, 11, and 14) exhibited evident antibacterial activity.

Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013.

PURPOSE: The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized. METHODS AND MATERIALS: Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival. RESULTS: Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and >5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (≥50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival. CONCLUSION: This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

A new epipolythiodioxopiperazine with antibacterial and cytotoxic activities from the endophytic fungus Chaetomium sp. M336.

A new compound 6-formamide-chetomin (1) together with chetomin (2) was isolated from solid fermentation products of the endophytic fungus Chaetomium sp. M336, which were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, and HR-ESI-MS experiments. The bioassay result showed that compound 1 had strong antibacterial activity against Escherichia coli, Staphylococcus aureus, Salmonella typhimurium ATCC 6539 and Enterococcus faecalis with minimum inhibitory concentration (MIC) value of 0.78 µg/mL; meanwhile it exhibited strong cytotoxicity with IC50 values of 21.6-27.1 nM against cell lines HeLa, SGC-7901 and A549.

Four new steroids from the endophytic fungus Chaetomium sp. M453 derived of Chinese herbal medicine Huperzia serrata.

An endophytic fungus, Chaetomium sp. M453, was isolated from Huperzia serrata (Thunb. ex Murray) Trev. and subjected to phytochemical investigation. Three unusual C25 steroids, neocyclocitrinols E-G (1-3), and 3ß-hydroxy-5,9-epoxy-(22E,24R)-ergosta-7,22-dien-6-one (4) together with three known steroids were isolated from solid fermentation products of the fungus, which were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-ESI-MS experiments. The absolute configuration of 1 was determined by X-ray crystallographic analysis and CD analyses. The acetylcholinesterase inhibitory activities of compounds 1-4 were tested in vitro. Compound 4 showed weak acetylcholinesterase inhibitory activity.

A new agent developed by biotransformation of polyphyllin VII inhibits chemoresistance in breast cancer.

Biotransformation by the endophytes of certain plants changes various compounds, and this 'green' chemistry becomes increasingly important for finding new products with pharmacological activity. In this study, polyphyllin VII (PPL7) was biotransformed by endophytes from the medicinal plant Paris polyphylla Smith, var. yunnanensis. This produced a new compound, ZH-2, with pharmacological activity in vitro and in vivo. ZH-2 was more potent than PPL7 in selectively killing more chemoresistant than chemosensitive breast cancer cells. ZH-2 also re-sensitized chemoresistant breast cancer cells, as evidenced by the improved anti-cancer activity of commonly-used chemotherapeutic agent in vitro, in vivo, and in clinical samples. This anti-chemoresistance effect of ZH-2 was associated with inhibiting the epithelial-mesenchymal transition (EMT) pathway. Taken together, our findings are the first one to link biotransformation with a biomedicine. The results provide insights into developing new pharmacologically-active agents via biotransformation by endophytes.

Progress in the treatment of pulmonary metastases after liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation (LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment (chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy (radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.

R237 and h238 are key amino acids in the rubella virus E1 neutralization epitope.

Residues 221-239 of rubella virus E1 glycoprotein contain antibody neutralization domains, and the solvent-exposed charged amino acids at the binding interface may be crucial for binding ability. However, the role of charged amino acid residues on the E1 epitope in peptide-antibody binding is unknown. To investigate the role of single amino acid substitutions on the important neutralizing epitope, biolayer interferometry and serological tests were performed. There are three charged residues in the neutralizing epitope: D229, R237, and H238. Substitution of D229 for amino acid A had no influence on the binding activity of the antibody to the peptide. However, substitutions of R237 or H238 for charged amino acid H or R were found to abolish the binding activity. Furthermore, substitution of an uncharged amino acid Q236 for a charged amino acid D was found to reduce the binding activity significantly. Thus, R237 and H238 are key amino acids in the rubella virus E1 neutralization epitope.

Castleman disease of the neck: CT and MR imaging findings.

OBJECTIVE: To characterize the computed tomography (CT) and magnetic resonance imaging (MRI) findings of Castleman disease of the neck. METHODS: The imaging findings of 21 patients with Castleman disease of the neck were reviewed retrospectively. Of the 21 patients, 16 underwent unenhanced and contrast-enhanced CT scans; 5 underwent unenhanced and contrast-enhanced MRI scans. RESULTS: The unenhanced CT images showed isolated or multiple well-defined homogenous mild hypodensity lesions in fifteen cases, and a heterogeneous nodule with central areas of mild hypodensity in one case. Calcification was not observed in any of the patients. In five patients, MR T1-weighted images revealed well-defined, homogeneous isointense or mild hyperintense lesions to the muscle; T2-weighted images showed these as intermediate hyperintense. Sixteen cases showed intermediate to marked homogeneous enhancement on contrast-enhanced CT or MR T1-weighted images. Of the other five cases that underwent double-phase CT scans, four showed mild or intermediate heterogeneous enhancement at the arterial phase, and homogeneous intermediate or marked enhancement at the venous phase; the remaining case showed mild and intermediate ring-enhancement with a central non-enhanced area at the arterial and venous phases, respectively. CONCLUSION: Castleman disease of the neck can be characterized as solitary or multiple well-defined, mild hypodensity or homogeneous intense lesions on plain CT/MR scans, and demonstrates intermediate and marked enhancement on contrast-enhanced CT/MR scans. On double-phase CT scans, Castleman disease often demonstrates mild enhancement at the arterial phase, and gradually uniform enhancement at venous phase. Double-phase enhanced CT or MRI may help to differentiate Castleman disease from other diseases.

Computed tomography and magnetic resonance imaging findings of inflammatory myofibroblastic tumors of the head and neck.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare tumor of mesenchymal origin that commonly occurs in the lung. Because of its non-specific clinical and imaging features, IMT is often misdiagnosed as a malignant tumor. There have been few imaging reports on IMT of the head and neck. PURPOSE: To analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of inflammatory myofibroblastic tumors (IMTs) of the head and neck. MATERIAL AND METHODS: Six patients with IMTs of the head and neck confirmed by histopathologic examination were analyzed retrospectively. RESULTS: The mean patient age was 40 years. The tumor locations in the six patients were as follows: left bridge of the nose (one), right infratemporal fossa (two), and left parotid gland (three). Three patients who underwent CT all had soft tissue masses or nodules and no calcification. Bridge of the nose tumor showed a homogeneous isodense nodule and mild homogeneous enhancement. Infratemporal fossa tumor showed a homogeneous low density mass and intermediate homogeneous enhancement. Left parotid gland tumor showed a heterogeneous, mostly low density mass, and intermediate heterogeneous enhancement. T1-weighted images of the parotid gland tumors were hypointense; the infratemporal fossa tumor was isointense. T2-weighted images were mildly hypointense and of mixed hypo- and isointensity in the two parotid gland tumors; the infratemporal fossa tumor was homogeneously mildly hypointense. Heterogeneous intermediate enhancement was demonstrated in one parotid gland and the infratemporal fossa patients and mild homogeneous enhancement in another parotid gland patient. CONCLUSION: The imaging features of IMTs of the head and neck are non-specific. An ill-defined, aggressive mass and variable enhancement on CT and MRI may suggest the diagnosis of IMT. IMT should be included in the differential diagnosis of regional tumors.

Effects of magnetic nanoparticle of Fe3O4 on apoptosis induced by Gambogic acid in U937 leukemia cells.

This study was aimed to explore the potential therapy of Gambogic acid (GA) combined with magnetic nanoparticle of Fe3O4 (Fe3O4-MNP) on leukemia. The proliferation of U937 cells and the cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscopy and flow cytometry respectively. The expressions of gene and protein were detected by quantitative real-time polymerase chain reaction and Western blot respectively. The results showed that GA enhanced the cytotoxicity for U937 cells in dose- and time-dependent manners. The Fe3O4-MNP itself had not cytotoxicity, but could enhance the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of U937 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA alone. The typical apoptotic features of cells treated with GA and Fe3O4-MNP were observed. The expression levels of caspase-3 and bax after co-treatment of GA and Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the expressions of bcl-2, NF-kappaB and survivin were down-regulated. It is concluded that Fe3O4-MNP can promote GA-induced apoptosis in U937 cells, and the combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for leukemia.

Clinical significance of vascular endothelial growth factor and connexin43 for predicting pancreatic cancer clinicopathologic parameters.

Vasiformation is essential for the growth and metastasis of tumor. Vascular endothelial growth factor (VEGF) and connexin43 (Cx43) are important regulatory factors of vasiformation. This study aimed to find out the expression features of VEGF and Cx43 and their significance in pancreatic cancer. The expression levels of VEGF and Cx43 protein in the samples, which came from 100 patients of human pancreatic cancer tissues and adjacent normal pancreatic tissues, were examined by using immunohistochemical streptavidin-peroxidase (S-P) method, Western-blotting, and RT-PCR analyses. Compared with adjacent normal pancreatic tissues, RT-PCR showed that the expression of VEGF mRNA was significantly higher in pancreatic cancer tissues (0.788±0.290, P<0.01) and Cx43 mRNA was significantly lower in pancreatic cancer tissues (0.403±0.204, P<0.01). The expression of VEGF protein was higher in pancreatic cancer tissue (0.745±0.254, P<0.01) by Western-blot, and Cx43 protein was obviously lower in pancreatic cancer tissues (0.373±0.164, P<0.01). The immunohistochemical S-P method showed as follows: the positive expression rate of VEGF and Cx43 protein was 77 and 48% in pancreatic cancer tissues and 15 and 100% in adjacent normal pancreatic tissues; expressions of VEGF were related to tumor size, TNM stage, and lymph node metastasis (P<0.05); there was a close relation between the expression of Cx43 and histological grades, TNM stage, and lymph node metastasis (P<0.05). This present study suggests that VEGF is overexpressed and the expression of Cx43 is lower in pancreatic cancer. The expression of VEGF and Cx43 is significantly correlated with TNM stage and lymph node metastasis. Furthermore, VEGF and Cx43 may play an important role in the occurrence, development, and metastasis of pancreatic cancer. To examine VEGF and Cx43 may be of value in judging the malignancy degree and the prognosis of pancreatic cancer.

[Reversal effect of Fe3O4-magnetic nanoparticles on multi-drug resistance of ovarian carcinoma cells and its correlation with apoptosis-associated genes].

BACKGROUND AND OBJECTIVE: Resistance to cisplatin (DDP) remains a major obstacle for the successful treatment of ovarian cancer. This study was to determine the reversal effect of Fe3O4-magnetic nanoparticles (MNPs) on DDP-resistance of ovarian carcinoma cell line SKOV3/DDP, and to explore its correlation with apoptosis-associated genes. METHODS: SKOV3/DDP cells were divided into the DDP group, the Fe3O4-MNPs group, the combination (DDP plus Fe3O4-MNPs) group, and the control group. Cell proliferation was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry (FCM). Intracellular DDP level was detected by inductively coupled plasma atomic emission spectrometry (ICP-AES). The expressions of apoptosis-associated genes, bcl-2, and survivin were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fe3O4-MNPs reversed DDP-resistance of SKOV3/DDP cells by 2.259 folds. The cell apotosis rate and the intracellular DDP level were significantly higher in the combination group than in the DDP group (P<0.05). Moreover, the mRNA levels of bcl-2 and survivin were significantly lower in the combination group than in the DDP group(P<0.05). CONCLUSIONS: Fe3O4-MNPs can reverse the DDP resistance of ovarian carcinoma SKOV3/DDP cells, and the effect may be ascribed to the down-regulation of bcl-2 and survivin expression.

MDR reversal activity of bromotetrandrine in vitro and in vivo.

The present study was aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet) in vitro and in vivo. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The ADM accumulation and the protein levels of P-glycoprotein (P-gp) were detected by flow cytometry. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of BrTet and Tet was investigated by using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. The results showed that BrTet at 0.25, 0.5 and 1 micromol/L reversed the resistance to ADM in MDR K562/A02 cells in a dose-dependent manner. Flow cytometry suggested that BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in K562/A02 cells, and down-regulated mdr1 expression. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, intraperitoneal injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of K562/A02 xenografts only by 5.8%. No enhancement effect by BrTet was seen in K562 xenografts. It is concluded that BrTet shows significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase intracellular accumulation of anticancer drugs. BrTet may be a promising-MDR modulator for eventual assessment in the clinic.

DcR3 and survivin are highly expressed in colorectal carcinoma and closely correlated to its clinicopathologic parameters.

OBJECTIVE: To investigate the expression of death decoy receptor 3 (DcR3) and survivin in colorectal carcinoma. METHODS: Tumor and normal tissues were taken from a total of 100 colorectal carcinoma patients during surgery, and the expression of DcR3 and survivin was examined by immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analyses. RESULTS: RT-PCR showed that the expression levels of DcR3 mRNA (0.846+/-0.242, P<0.01) and survivin mRNA (0.7835+/-0.2392, P<0.01) in colorectal cancer tissues were significantly higher than those in adjacent normal tissues. Western blotting showed that the expression levels of DcR3 protein (0.795+/-0.261, P<0.01) and survivin protein (0.6765+/-0.1351, P<0.01) in tumor tissues were significantly higher than those in non-cancer tissues. The immunohistochemical streptavidin-peroxidase (SP) method showed that the positive expression rates of DcR3 and survivin were 67.0% and 58.0% in colorectal cancer tissues, and 18.0% and 3.0% in non-cancerous colorectal tissues (P<0.05), respectively. The positive correlations of DcR3 (P<0.01) and survivin (P<0.01) to the differentiation of colorectal carcinoma cells, lymph node metastasis, and pathological stage were observed. The expression of DcR3 and survivin was found to be positively correlated to clinicopathologic parameters of colorectal carcinoma. CONCLUSION: The overexpressed DcR3 and survivin in colorectal cancer may contribute to the development of the cancer. The monitoring of these two proteins may be useful for the diagnosis, differentiation, metastasis, and determination of stages of colorectal carcinoma.

Daunorubicin-loaded magnetic nanoparticles of Fe(3)O(4) greatly enhance the responses of multidrug-resistant K562 leukemic cells in a nude mouse xenograft model to chemotherapy.

Multidrug resistance (MDR) plays a major role in the failure of cancer chemotherapy. Since Fe(3)O(4)-magnetic nanoparticle loaded with daunorubicin (DNR) can overcome multidrug-resistance of K562 cells in vitro, the effect of Fe(3)O(4)-magnetic nanoparticle loaded with DNR on multidrug-resistant K562 cells was studied in vivo, the K562-n and its MDR counterpart K562-n/VCR cells were inoculated subcutaneously into both sides of the back of nude mice to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline, group B receiving DNR, group C receiving Fe(3)O(4)-magnetic nanoparticle, group D receiving Fe(3)O(4)-magnetic nanoparticle loaded with DNR and group E receiving Fe(3)O(4)-magnetic nanoparticle containing DNR with a magnetic field built on the surface of the tumor tissue. The tumor volume was measured on the day 1, 5, 9, 13, 17 and 21 after the first treatment. Tumor tissues were isolated for examination of the expression of mdr-1 by reverse transcription polymerase chain reaction and Western blotting. The results showed that for K562-n/VCR tumor, the tumor volume was markedly lower in groups D and E than that in groups A, B and C. Pathological observation revealed that the tumor cells of group A and B grew well, some disseminated necrosis and some cells with karyorrhexis and karyopyknosis existed in group C. However, significant fracture, necrosis of cell and subsequently fibrosis were seen in group D and E. The transcription of mdr-1 gene in groups D and E was significantly lower than that in groups A, B and C (group D and E vs group A, B or C, p < 0.05). However, there were no differences about the protein expression of P-gp between these groups. The tumor volume of K562-n in groups C, D and E was markedly lower than that in groups A and B (group C, D and E vs group A or B, p < 0.05). Pathological observation showed that the tumor cell of group A and B grew well, and no obvious necrosis was observed. Significant fracture, necrosis of cell and subsequently fibrosis were seen in group C, D and E. It is concluded that DNR-loaded Fe(3)O(4) magnetic nanoparticles can suppress the growth of the MDR K562-n/VCR tumor in vivo, but can not further enhance its efficacy on the sensitive K562-n tumor as compared to DNR alone. The additional external magnetic field failed to further improve the antitumor effect in vivo.

Effects of magnetic nanoparticle of fe(3)o(4) and 5-bromotetrandrine on apoptosis of K562/A02 leukemic cells induced by daunorubicin.

The aim of this study was to investigate the potential benefit of combination therapy with magnetic nanoparticle of Fe(3)O(4) and 5-Bromotetrandrine (5-BrTet) on chronic leukemia. The apoptosis was detected by flow cytometry (FCM), Wright staining and light microscope; the expressions of BAX and BCL-2 were measured by Western blot. The results showed that combination of daunorubicin (DNR) with either MNP (Fe(3)O(4)) or 5-BrTet exerted a potent cytotoxic effect on K562/A02 cells, while MNP (Fe(3)O(4)) and 5-BrTet co-treatment could synergistically enhance DNR-induced apoptosis. After treated with this regimen, the typical apoptotic morphological features were found in K562/A02 cells; the expression level of BCL-2 decreased and BAX increased markedly. It is concluded that MNP (Fe(3)O(4)) or 5-BrTet with DNR can induce apoptosis in K562/A02 cells, and they show distinct synergism when used together. The down-regulation of BCL-2 and the up-regulation of BAX may play important roles.