FLOT Neoadjuvant Chemotherapy Followed by Laparoscopic D2 Gastrectomy in the Treatment of Locally Resectable Advanced Gastric Cancer.

Background: The prognosis of patients with advanced gastric cancer remains unsatisfactory, highlighting the need for improved therapeutic strategies. We analyzed 23 resectable advanced gastric cancer patients who received FLOT followed by laparoscopic gastrectomy with D2 lymphadenectomy to evaluate the efficacy and safety. Methods: Patients aged 18-75 years with gastric adenocarcinoma (stage cT3-4 and/or N + M0) underwent neoadjuvant FLOT therapy (four preoperative and four postoperative 2-week cycles) at Shanghai East Hospital. Laparoscopic gastrectomy was scheduled 3-4 weeks after completion of the last cycle of preoperative chemotherapy. The type of surgical procedure was determined by the location and extent of the primary tumor. Results: 23 patients were reviewed in the study. 20 patients (81.2%) received four courses of FOLT therapy, while 3 patients (18.8%) received three courses of treatment. There were 3 (13.0%) complete responses, 13 (56.5%) partial responses, 4 (26.1%) of stable disease, and 1 (4.3%) of progressive disease. The clinical efficacy response rate was 69.6%. The R0 resection rate was 91.3%. Only one patient exhibited grade III postoperative complications. The pathologic complete remission was 13%. The common grade 3/4 adverse events from chemotherapy were leucopenia (17.4%), neutropenia (30.4%), anemia (13%), anorexia (13%), and nausea (17.4%). Postoperative complications occurred in 5 patients (26.1%). There was no treatment-related mortality or reoperation. The most reason for not completing chemotherapy was the patient's request. Conclusions: These findings suggest that FLOT neoadjuvant chemotherapy, followed by laparoscopic D2 gastrectomy, is effective and safe in advanced, resectable advanced gastric cancer.

Changes of hippocampus proteomic profiles after blueberry extracts supplementation in APP/PS1 transgenic mice.

Objective: To examine protein changes in the hippocampus of APP/PS1 transgenic mice after blueberry extracts (BB) intervention.Methods: Eight APP/PS1 transgenic mice were randomly assigned to Alzheimer's disease (AD)+BB group (n=4) and AD+control group (n=4). After a 16-week treatment, 2-DE and MALDI-TOF-MS were used to compare the proteomic profiles of the hippocampus in the two groups and Western blot was used to confirm the important differentially expressed proteins.Results: Twelve proteins were differentially expressed between the two groups. Nine of them were identified. Cytochrome b-c1 complex subunit 6, beta-actin, dynamin 1, and heat shock cognate 71 were up-regulated in AD+BB group, while a-enolase, stress-induced-phosphoprotein 1, malate dehydrogenase (MDH), MDH 1, and T-complex protein 1 subunit beta were down-regulated, respectively. Importantly, some of the identified proteins (e.g. dynamin 1) are known to be involved in cognitive impairment. Western blot analysis of hippocampus dynamin 1 expression confirmed the proteomic findings.Conclusions: The consumption of BB modulates the expression of proteins that are linked to the improvements of cognitive dysfunction in hippocampus of APP/PS1 transgenic mice.

Investigation on the Role of BDNF in the Benefits of Blueberry Extracts for the Improvement of Learning and Memory in Alzheimer's Disease Mouse Model.

BACKGROUND: Blueberry (BB) can provide a wide range of antioxidant benefits for AD. There is evidence that BB extracts could improve brain functions. However, the details are still unknown. OBJECTIVE: In the present study, we aimed to investigate the possible mechanism involved in the improvement of learning and memory capacity from BB extracts in AD. METHODS: APP/PS1 transgenic mice were fed BB extracts for 16 weeks. The capacity of learning and memory was assessed by Morris water maze (MWM) test, and long-term potentiation (LTP) was determined to evaluate hippocampal neuronal plasticity at the end of administration. Pathological changes in the brain were observed, and the expressions of brain-derived neurotrophic factor (BDNF) and extracellular signal-related kinase (ERK1/2) were determined to explore the mechanism of BB extract-induced benefits. RESULTS: AD mice exhibited more difficulties to learn and remember the exact position of the platform in the MWM test. The data showed that AD mice lacked effective learning in the platform search. In contrast, AD mice exhibited better performance both in the training phase and probe test of MWM after the BB treatment. Moreover, LTP was enhanced and the neuron loss was alleviated with BB treatment, while we did not find any obvious effect on the elimination of amyloid-ß. In the AD mice, the expression of ERK1/2 was significantly increased (p < 0.05), while the level of BDNF was decreased (p < 0.05). CONCLUSIONS: BB treatment was beneficial for the improvement of learning and memory of AD, and these effects might be related to the regulation of BDNF.

Mulberry extracts alleviate aß 25-35-induced injury and change the gene expression profile in PC12 cells.

Mulberry, which contained high amounts of anthocyanins, has been used in traditional Chinese medicine. Mulberry fruit extracts (ME) have demonstrated the antioxidant activity and neuroprotection. The study was to investigate the neuroprotective efficacy of ME against ß-amyloid 25-35- (Aß 25-35-) induced PC12 cells injury. Cells preincubated with or without ME (200 µg/mL) for 24 h were treated with Aß 25-35 (20 µmol/L) for another 24 h. Cell viability was assessed by MTT, gene expression profiles were examined by cDNA microarrays, and RT-PCR were used to confirm the results of microarray assays. ME pretreatment was found to neutralize the cytotoxicity and prevent Aß 25-35-induced cells injury. Analyses of gene expression profile revealed that genes involving cell adhesion, peptidase activity, cytokine activity, ion binding activity, and angiogenesis regulation were significantly modulated by ME pretreatment. Among those genes, Apaf1, Bace2, and Plcb4 were enriched in the "Alzheimer's disease-reference pathway" and downregulated after ME intervention. RT-PCR results showed that ME preincubation could significantly inhibit Aß 25-35 increased mRNA levels of these three genes. Overall, ME pretreatment could substantially alleviate PC12 cells injury and downregulate expression of AD-related genes, such as Apaf1, Bace2, and Plcb4. This study has a great nutrigenomics interest and brings new and important light in the field of AD intervention.

[Primary study on protective effect of mulberry extracts on Abeta25-35-induced PC12 cells injury].

OBJECTIVE: To investigate the neuroprotective effect of mulberry extracts (ME) against Abeta25-35-induced injury in cultured PC12 cells and explore the possible mechanisms involved. METHODS: PC12 cells at logarithmic growth phase were divided into the normal control group, Abeta25-35 group (20 micromol/L for 24h) and ME pretreating groups at the concentrations of 25, 50, 100, 200, 400, 800 microg/ml. Cell viability was determined by MTT assay. On that basis, PC12 cells were divided into the normal control group, ME group (200 microg/ml ME incubation alone for 24h), Abeta25-35 group (20 micromol/L for 24h) and ME plus Abeta25-35 group (after pretreatment with 200 microg/ml ME for 24h, cells were exposed to 201 micromol/L Abeta25-35 for another 24h). Intracellular reactive oxidative species (ROS) was measured by using the fluorescent DCFH-DA and the apoptotic cells were observed by Hoechst33342 staining method. RESULTS: (1) The results showed that exposure of PC12 cells to Abeta22-35 (20 micromol/L) for 24h induced notably neuronal injury (P < 0.05) as compared with the control group, while pretreatment with 100 or 200 microg/ml ME almost completely reversed Abeta25-35 induced neuronal injury (P < 0.05). (2) There were no remarkable changes in ROS levels and apoptosis rate of ME group as compared with the control group (P > 0.05). Compared with the control group, exposure to 20 micromol/L Abeta25-35 for 24h resulted in a significant decrease in cell viability (P < 0.05) while increase in ROS levels and cell apoptosis rate (P < 0.05). But pretreatment of PC12 cells with 200 microg/ml ME could counteract ROS formation and inhibit apoptosis (P < 0.05). CONCLUSION: These results suggest that mulberry extracts rich in phenolics and anthocyanins could alleviate Abeta25-35-induced injury in PC12 cells, which might be associated with the antioxidative and antiapoptosis effects.