Curcumin-encapsulated fish gelatin-based microparticles from microfluidic electrospray for postoperative gastric cancer treatment.

Gastric cancer is the fifth most frequently diagnosed malignant neoplasm and the third leading cause of cancer-related mortality. Nevertheless, the therapeutic efficacy of conventional surgical and chemotherapeutic interventions in clinical practice is often unsatisfactory. Curcumin (Cur) has shown promise as a therapeutic agent in prior studies. However, its progress in this context has been impeded by challenges including low solubility, instability in aqueous environments, and rapid metabolism. In this study, we develop methacrylate fish gelatin (FGMA) hydrogel microparticles (FGMPs@Cur) encapsulating Cur via microfluidic electrospray technology for postoperative comprehensive treatment of gastric cancer. Comprehensive characterizations and analyses were conducted to assess the cytotoxicity against gastric cancer cells and potential tissue reparative effects of FGMPs@Cur. In vitro experiments revealed that FGMPs@Cur exhibited a remarkable cytotoxic effect on nearly 80 % of gastric cancer cells while maintaining at least 95 % viability of normal cells in cell compatibility tests. In vivo results demonstrated that FGMPs@Cur significantly reduced tumor volume to 47 % of the control group, and notable tissue regeneration was observed at the surgical site. These properties indicated that such a hydrogel microparticle system is a promising candidate for postoperative gastric cancer treatment in practical application.

An autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer.

Multicomponent deoxyribozymes (MNAzymes) have great potential in gene therapy, but their ability to recognize disease tissue and further achieve synergistic gene regulation has rarely been studied. Herein, Arginylglycylaspartic acid (RGD)-modified Distearyl acylphosphatidyl ethanolamine (DSPE)-polyethylene glycol (PEG) (DSPE-PEG-RGD) micelle is prepared with a DSPE hydrophobic core to load the photothermal therapy (PTT) dye IR780 and the calcium efflux pump inhibitor curcumin. Then, the MNAzyme is distributed into the hydrophilic PEG layer and sealed with calcium phosphate through biomineralization. Moreover, RGD is attached to the outer tail of PEG for tumor targeting. The constructed nanomachine can release MNAzyme and the cofactor Ca2+ under acidic conditions and self-assemble into an active mode to cleave heat shock protein (HSP) mRNA by consuming the oncogene miRNA-21. Silencing miRNA-21 enhances the expression of the tumor suppressor gene PTEN, leading to PTT sensitization. Meanwhile, curcumin maintains high intracellular Ca2+ to further suppress HSP-chaperone ATP by disrupting mitochondrial Ca2+ homeostasis. Therefore, pancreatic cancer is triple-sensitized to IR780-mediated PTT. The in vitro and in vivo results show that the MNAzyme-based nanomachine can strongly regulate HSP and PTEN expression and lead to significant pancreatic tumor inhibition under laser irradiation.

Elemene Induces Apoptosis of Human Gastric Cancer Cell Line BGC-823 via Extracellular Signal-Regulated Kinase (ERK) 1/2 Signaling Pathway.

BACKGROUND Elemene is extracted from a traditional herbal medicine and is commonly used in the treatment of cancer in China. However, its effect on gastric cancer cells remains unknown. The goal of this study was to investigate its effect on human gastric cancer cells. MATERIAL AND METHODS Human gastric cancer BGC-823 cells and a tumor-bearing mouse model were employed to be divided into 4 groups: control group, elemene group, PD98059 group (an ERK 1/2 signaling pathway inhibitor), and the combined group (elemene plus PD98059). The tumor size, cell proliferation, expression of ERK 1/2 and phosphorylated ERK 1/2 (p-ERK 1/2), Bcl-2 mRNA, and Bax mRNA were measured. Moreover, cell apoptosis was detected and the apoptosis index was calculated. RESULTS Elemene and PD98059 each significantly inhibited the proliferation of gastric cancer cells BGC-823, and their combination showed higher synergistic inhibitory effect (P<0.05). We also found increased expression levels of p-ERK l/2 protein and Bax mRNA, but reduced level of Bcl-2 mRNA expression (P<0.05). Elemene presented higher apoptosis rate in a dose-dependent manner (P<0.05). Furthermore, the injection of elemene decreased the weight of transplanted tumors. CONCLUSIONS Elemene can inhibit the proliferation and induce the apoptosis of gastric cancer cells associated with the ERK 1/2 signaling pathway and expression levels of Bax mRNA and Bcl-2 mRNA.

Efficacy of docetaxel combined with oxaliplatin and fluorouracil against stage III/IV gastric cancer.

AIM: To investigate the clinical efficacy and toxic effects of neoadjuvant chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for treating stage III/IV gastric cancer. METHODS: A total of 53 stage III/IV gastric cancer patients were enrolled into the study and treated with neoadjuvant chemotherapy. Two of the cases were excluded. The program was as follows: 75 mg/m(2) docetaxel and 85 mg/m(2) oxaliplatin on day 1 and 1500 mg/m(2) fluorouracil on days 1 to 3 for three weeks. RESULTS: The tumour changes, postoperative remission rate, changes in the symptoms and adverse reactions were observed. The overall clinical efficacy (complete remission + partial remission) of the neoadjuvant chemotherapy was 62.7%. R0 radical resection was performed on 60.8% of the patients, with a remission rate (pathological complete response + pathological subtotal response + pathological partial response) of 74.2%. The Karnofksy score improved in 42 cases. The toxicity reactions mostly included myelosuppression, followed by gastrointestinal mucosal lesions, nausea, vomiting and diarrhoea. CONCLUSION: Neoadjuvant chemotherapy consisting of docetaxel combined with oxaliplatin and fluorouracil is effective for stage III/IV gastric cancer. However, the treatment is associated with a high incidence of bone marrow suppression, which should be managed clinically.