Gene expression and apoptosis response in hepatocellular carcinoma cells induced by biocompatible polymer/magnetic nanoparticles containing 5-fluorouracil

BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.

Toxicity of Chemotherapeutics Based on Viscera-state doctrine / 中国实验方剂学杂志

Malignant tumors are important diseases that threaten human health. Although targeting and immunotherapy have been gradually applied in the treatment of malignant tumors in recent years， which can alleviate the suffering of patients to a certain extent， there are still problems of large adverse reactions and easy drug resistance. At present， chemotherapy is still the main method for the treatment of malignant tumors. While killing tumor cells， chemotherapy also damages normal cells， which often leads to drug toxicity， such as bone marrow suppression， gastrointestinal adverse reactions， liver and kidney function damage， and oral mucosal reactions. Although modern medicines have a certain effect on the toxicity of chemotherapy drugs， there are still limitations. Traditional Chinese medicine（TCM） has a long history of treating malignant tumors， and considers that chemotherapy is a drug with toxin invading the body， exacerbating the "deficiency"， "toxin" and "stasis" of the body， causing damage to Qi， blood and organs， especially in spleen， stomach， liver and kidney， and leading to bone marrow suppression， liver and kidney function injury and other adverse reactions. Studies have confirmed that the use of TCM treatment has a better clinical efficacy. Therefore， new therapies shall be explored based on the basic theory of traditional Chinese medicine. As the core part of the theoretical system of TCM， Viscera-state doctrine is closely related to looking， listening， questioning and feeling the pulse of TCM， and has constantly developed and improved. It has important significance in guiding diagnosis and treatment of diseases. This study is guided by viscera-state doctrine of TCM and based on the etiology and pathogenesis of TCM. It starts with the clinical manifestations of common drug toxicity of chemotherapy drugs， such as bone marrow suppression， gastrointestinal adverse reactions， liver and kidney function damage， oral mucosal reactions， which are external signs of the toxicity of chemotherapeutic drugs， and associates pathological manifestations of viscera to physiological functions. From elephants and Tibetans， it systematically summarizes the viscera characteristics of various common chemotherapeutic drugs and provides new ideas and methods for clinical use of TCM in treating the toxicity of chemotherapeutic drugs， so as to promote the application of viscera-state doctrine in diagnosis and treatment of diseases.

Progress of Gut Microbiota in the Antineoplastic Efficacy of Chemotherapeutic Drugs / 中国药学杂志

Chemotherapeutic drugs play an important role in the treatment of cancer, but the individual differences of patients' sensitivity to chemotherapeutic drugs and the drug resistance of chemotherapeutic drugs have always been a thorny problem in clinical treatment. Recent studies have shown that gut microbiota plays a key role in regulating the efficacy of chemotherapeutic drugs. Gut microbiota can regulate host response to chemotherapy through a variety of mechanisms, including immune interaction, heterogeneous metabolism and changes in community structure. This paper introduces the effects of traditional chemotherapeutic drugs and new immunotherapeutic drugs, such as anti-CTLA-4 and anti-PD-1 antibodies, on gut microbiota, as well as their effects on chemotherapeutic efficacy and mechanism, in order to provide evidences and clues for cancer treatments targeting gut microbiota.

A Review of Modeling Approaches to Predict Drug Response in Clinical Oncology

Model-based approaches have emerged as important tools for quantitatively understanding temporal relationships between drug dose, concentration, and effect over the course of treatment, and have now become central to optimal drug development and tailored drug treatment. In oncology, the therapeutic index of a chemotherapeutic drug is typically narrow and a full dose–response relationship is not available, often because of treatment failure. Noting the benefits of model-based approaches and the low therapeutic index of oncology drugs, in recent years, modeling approaches have been increasingly used to streamline oncologic drug development through early identification and quantification of dose–response relationships. With this background, this report reviews publications that used model-based approaches to evaluate drug treatment outcome variables in oncology therapeutics, ranging from tumor size dynamics to tumor/biomarker time courses and survival response.

Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems.

Chemo-sensitivity enhancing effects of Shengmai Injection on various chemotherapeutic drugs / 中草药

Objective: To investigate the chemo-sensitivity enhancing effect and its major active mechanism of Shengmai Injection (SMI). Methods: MTT assay was used to determine the chemo-sensitivity enhancing activity of SMI combined with various current- used chemotherapeutic drugs. Flow cytometry was conducted to determine the effect of Epirubicin combined with SMI on the cell cycle distribution and apoptotic cell death, and the mRNA expression level of MDR-1 gene was determined by RT-PCR. Results: SMI (30 μL/mL) combined with gemcitabine, cisplatin, paclitaxel, and Epirubicin exihibited the potent antiproliferative effects on human lung carcinoma A549, gastric carcinoma SGC-7901, breast carcinoma MCF-7, and hepatocellular carcinoma HepG-2 cell lines, respectively. SMI showed the most significant enhancing effects on HepG-2 cells in combination with Epirubicin, and the sensitivity of HepG-2 to Epirubicin was increased by 16 fold. Whereas SMI (30 μL/mL) alone did not affect the cell cycle distribution and apoptosis of HepG-2 cells, it enhanced the cellular responses when combined with Epirubincin together with a down-regulated mRNA level of MDR-1 gene. Conclusion: SMI combined with the different chemotherapeutic drugs could enhance the sensitivity of cancer cells significantly via down-regulating the mRNA expression level of MDR-1 and the expression of P-glucoprotein with the excretion of drugs.

Prevention of spillage by adding chemotherapeutic drugs into transfusion bottles under negative pressure / 中国实用护理杂志

ObjectiveThe purpose of the present study was to discuss the method to avoid spillage by means of adding chemotherapeutic drugs into sealed transfusion bottles.Methods90 penicillin sealed bottles of the same batch number were randomly divided into the test group and the control group,each with 45 bottles.Standard method according to Basic Nursing was used to add chemotherapeutic drugs into transfusion bottles in the control group.Drugs were added into transfusion bottles under negative pressure in the test group.The operating time was measured,the spillage volume of puncture site was calculated and microbial detection of syringe was observed in the two groups.ResultsThere was a significant difference in the spillage volume of puncture site between the two groups (P<0.01),but no difference was seen in the operating time and microbial detection of syringe (P>0.05),ConclusionsThe spillage volume of puncture site was reduced significantly by means of adding chemotherapeutic drugs into transfusion bottles under negative pressure.This can decrease chemotherapeutic professional exposing risks and drug wastage.

Combination treatment for osteosarcoma with baculoviral vector mediated gene therapy (p53) and chemotherapy (adriamycin)

The insect baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) has been evaluated as a vector for gene delivery to human tumor cells. A human osteogenic sarcoma cell line, Saos-2, was found to be highly susceptible to infection with a baculoviral vector, with nearly 100% of Saos-2 cells being able to express a lacZ reporter gene after a brief exposure to the virus at a m.o.i. of 30 pfu/cell. The production of beta-galactosidase protein was 18-times greater than that in HepG2 cells which were previously thought to be the mammalian cells most susceptible to the baculovirus. The possibility of developing a baculovirus as a cytotoxic vector for p53-defective cancer was tested by destruction of Saos-2 cells (p53-/-) with a recombinant baculovirus containing the wild type p53 gene (BV-p53) in vitro. The p53 baculovirus induced apoptotic cell death in tumor cells in a dose-dependent manner with approximately 60% killing at an m.o.i. of 160 pfu/cell. Combined treatments of gene therapy (p53) and chemotherapy (adriamycin) resulted in synergistic and potent killing of the osteogenic sarcoma cells. For example, greater than 95% of Saos-2 cells were killed by the combination of BV-p53 (m.o.i. of 100) and adriamycin (35 ng/ml), whereas approximately 50% and approximately 55% cells were killed by BV-p53 and adriamycin alone, respectively. These results indicate that a baculoviral gene delivery vector can be used to efficiently target certain types of mammalian cells and the combination treatment of gene-therapy mediated by a baculovirus and chemotherapy may enhance induction of apoptosis in cancer cells.

The Effects of All-trans and 13-cis Retinoic Acid on C6 Cell Line Cultures

Retinoic acid has been used as a trial of chemotherapeutic agent in the field of cancer therapy and resulted some success in leukemia and breast cancer. Recently, it is being tried on the malignant astrocytoma. We evaluated the effect of all-trans and 13 cis-retinoic acid on C6 cell line cultures(14 day incubation) using MTT assay and counting of cell numbers for establishing the basis of clinical trial. The cell number counting showed 51.6% and 43.1% of control in the cell number at 10 -6M concentration of all-trans and 13 cis-retinoic acid. MTT assay showed 56.4% and 46.1% of control in the optical absorbance at 10 -6M concentration of all-trans and 13 cis-retinoic acid. These results indicate the possiblity of both drug as effective chemotherapeutic agents for glial cell tumors but in-vivo study will be needed for clinical trial.